Archives of Pharmacal Research

  • 제27권7호
  • /
  • Pages.693-712
  • /
  • 2004
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Pharmacokinetic Changes in Drugs during Protein-Calorie Malnutrition： Correlation between Drug Metabolism and Hepatic Microsomal Cytochrome P450 Isozymes

  • Lee, Joo-Hyun (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University) ;
  • Suh, Ok-Kyung (Pharmacy Department, Long Beach Memorial Medical Cente) ;
  • Lee, Myung-Gull (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
  • 발행 : 2004.07.01
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초록

The rats with protein-calorie malnutrition (PCM, 5％ casein diet for a period of 4-week) were reported to exhibit 60 and 80％ suppression in the hepatic microsomal cytochrome P450 (CYP) 1 A2 and CYP2C11 levels, respectively, and 40-50％ decreases in CYP2E1 and CYP3A 1/2 levels compared to control (23％ casein diet for a period of 4-week) based on Western blot analysis. In addition, Northern blot analysis showed that CYP1 A2, CYP2E1, CYP2C11, and CYP3A1/2 mRNAs decreased in the state of PCM as well. Hence, pharmacokinetic changes of the drugs in rats with PCM [especially the area under the plasma concentration-time curve from time zero to time infinity (AUC) changes of metabolite(s)] reported from literatures were tried to explain in terms of CYP isozyme changes in the rats. Otherwise, the time-averaged nonrenal clearance ($CL_{NR}$) of parent drug was compared. Pharmacokinetic changes of the drugs in other types of malnutritional state, such as kwashiorkor and marasmus, in both human and animal models were also compared. The drugs reviewed are as follows： diuretics, antibiotics, anticancer agents, antiepileptics, antiarrythmics, analgesics, xanthines, antimalarials, and miscellaneous.

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참고문헌

  1. Adelusi, S. A. and Salako, L. A., The effect of protein-energy malnutrition on the absorption, distribution and elimination of chloroquine in the rat. Gen. Pharmacol., 13, 505-509 (1982) https://doi.org/10.1016/0306-3623(82)90025-8
  2. Ahn, C. Y., Kim, E. J., Kwon, J. W, Chung, S. J., Kim, S. G., Shim, C.-K., and Lee, M. G., Effects of cysteine on the pharmacokinetics of intravenous clarithromycin in rats with protein-calorie malnutrition. Life Sci., 73, 1783-1794 (2003) https://doi.org/10.1016/S0024-3205(03)00540-X
  3. Akinyinka, O. O., Sowunmi, A, Honeywell, R., and Renwick, A. G., The pharmacokinetics of caffeine in Nigerian children sufterinq from malaria and kwashiorkor. Eur. J. Glin. Pharmacol., 56, 153-158 (2000) https://doi.org/10.1007/s002280050734
  4. Anderson, K. E., Schneider, J., Pantuck, E. J., Pantuck, C. B., MUdge, G. H., Welch, R. M., Conney, A. H., and Kappas, A, Acetaminophen metabolism in subjects fed charcoal-broiled beef. Glin. Pharmacol. Ther., 34, 369-374 (1983) https://doi.org/10.1038/clpt.1983.181
  5. Arunkumar, S. R. and Krishnaswamy, K., Metabolism of sulphadiazine in malnutrition. Br. J. Glin. Pharmacol., 7, 69-73 (1979) https://doi.org/10.1111/j.1365-2125.1979.tb00899.x
  6. Asano, T., Inoue,T., and Kurono, M., Disposition of azosemide. I. Distribution, metabolism and excretion following intravenous administration to rats. Yakugaku Zasshi, 104, 1181-1190 (1984)
  7. Ashton, M., Bolme, P., Alemayehu, E., Eriksson, M., and Paalzow, L., Decreased chloramphenicol clearance in malnourished Ethiopian children. Eur. J. Glin. Pharmacol., 45, 181-186 (1993a) https://doi.org/10.1007/BF00315503
  8. Bae, S. K., Lee, A. K., Kwon, J. W., Chung, S. J., Kim, S. G., Shim, C.-K., and Lee, M. G., Effects of cysteine on the pharmacokinetics of intravenous torasemide in rats with protein-calorie malnutrition. J. Pharm. Sci., in press(2004a)
  9. Bae, S. K., Chung, W.-S., Kim, E. J., Rhee, J. K., Kwon, J. W., Kim, W. B., and Lee, M. G., Pharmacokinetics of DA-7867, a new oxazolidinone, after intravenous or oral administration to rats: Intestinal first-pass effect. Antimicrob. Agents. Ghemother., 48, 659-662 (2004b) https://doi.org/10.1128/AAC.48.2.659-662.2004
  10. Bae, S. K., Lee, S. J., Kwon, J. W., Kim,W. B., and Lee, M. G., Effects of protein-calorie malnutrition on the pharmacokinetics of DA-7867, a new oxazolidinone, in rats. J. Pharm. Sci., in press(2004c)
  11. Bano, G., Raina, R. K., and Sharma, D. B., Pharmacokinetics of carbamazepine in protein-energy malnutrition. Pharmacology, 32, 232-236 (1986) https://doi.org/10.1159/000138174
  12. Beermann, B. and Grind, M., Clinicalpharmacokinetics of some newer diuretics. Clin. Pharmacakinet., 13, 254-266 (1987) https://doi.org/10.2165/00003088-198713040-00003
  13. Bergan, T., Ortengren, B., and Westerlund, D., Clinical pharmacokinetics of cotrimazine. Clin. Pharmacakinet., 11, 372-386 (1986) https://doi.org/10.2165/00003088-198611050-00003
  14. Bistrian, B. R., Blackburn, G. L., Hallowell, E., and Heddle, R., Protein status of general surgical patients. J. Am. Med. Assoc., 230, 858-860 (1974) https://doi.org/10.1001/jama.230.6.858
  15. Bistrian, B. R., Blackburn, G. L., Vitale, J., Cochran, D., and Naylor, J., Prevalence of malnutrition in general medical patients. J. Am. Med. Assac., 235, 1567-1570 (1976) https://doi.org/10.1001/jama.235.15.1567
  16. Bolme, P., Eriksson, M., Habte, D., and Paalzow, L., Pharmacokinetics of streptomycin in Ethiopian children with tuberculosis and of different nutritional status. Eur. J. Clin. Pharmacol., 33, 647-649 (1988) https://doi.org/10.1007/BF00542504
  17. Bolme, P., Eriksson, M., Paalzow, L., Stintzing, G., Zerihun, G., and Woldemariam, T., Malnutrition and pharmacokinetics of penicillin in Ethiopian children. Pharmacol. Toxicol., 76, 259-262 (1995) https://doi.org/10.1111/j.1600-0773.1995.tb00140.x
  18. Brater, D. C., Day, B., Anderson, S., and Seiwell, R., Azosemide kinetics and dynamics. Clin. Pharmacol. Ther., 34, 454-458 (1983) https://doi.org/10.1038/clpt.1983.197
  19. Bravo, I. G., Bravo, M. E., Plate, G., Merlez, J., and Arancibia, A, The pharmacokinetics of cotrimoxazole sulphonamide in malnourished (marasmic) infants. Pediatr. Pharmacol. (New York),4, 167-176 (1984)
  20. Bredberg, E. and Paalzow, L. K., Altered pharmacokinetics and dynamics of apomorphine in the malnourished rat: Modeling of the composed relationship between concentration and heart-rate response. Pharm. Res., 7, 318-324 (1990) https://doi.org/10.1023/A:1015850802006
  21. Bu, S. C., Kim, Y. G., Kim, S. H., and Lee, M. G., Effects of enzyme inducers and inhibitor on the pharmacokinetics of intravenous 2-(allylthio)pyrazine, a new chemoprotective agent, in rats. Biapharm. Drug Dlspos., 21, 157-164 (2000) https://doi.org/10.1002/1099-081X(200005)21:4<157::AID-BDD226>3.0.CO;2-C
  22. Buchanan, N., Drug kinetics in protein-energy malnutrition. S. Afr. Med. J., 53, 327-330 (1978)
  23. Buchanan, N., Davis, M. D., and Eyberg, C., Gentamicin pharmacokinetics in kwashiorkor. Br. J. Clin. Pharmacol., 8, 451-453 (1979a) https://doi.org/10.1111/j.1365-2125.1979.tb01024.x
  24. Buchanan, N., Eyberg, C., and Davis, M. D., Antipyrine pharmacokinetics and D-glucaric excretion in kwashiorkor. Am. J. Clin. Nutr., 32, 2439-2442 (1979b)
  25. Buchanan, N., Eyberg, C., and Davis, M. D., Isoniazid pharma-cokinetics in kwashiorkor. S. Atr. Med. J., 56, 299-300 (1979c)
  26. Buchanan, N., Robinson, R., Koornhof, H. J., and Eyberg, C.,Penicillin pharmacokinetics in kwashiorkor. Am. J. Clin. Nutr., 32, 2233-2236 (1979d)
  27. Butler, M. A, Iwasaki, M., Guengerich, F. P.,and Kadlubar, E E, Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc. Natl. Acad. Sci. U.S.A., 86, 7696-7700 (1989) https://doi.org/10.1073/pnas.86.20.7696
  28. Chambers, H. F., Chapter 47. Protein synthesis, inhibitors and miscellaneous antibacterial agents, In Goodman & Gilman, The Pharmacological basis of therapeutics. Hardman, J. G., Limbird, L. L., and Gilman, A. G., 10th (ed). Mc Graw-Hill, Medical Publishing Division, New York. p. 1242 (2001)
  29. Charland, S. L., Bartlett, D., and Torosian, M. H., Effect of protein-calorie malnutrition on methotrexate pharmacokinetics. J. Parenter. Enteral. Nutr., 18, 45-49 (1994) https://doi.org/10.1177/014860719401800145
  30. Chen, W., Koenigs, L. L., Thompson, S. J., Peter, R. M., Rettie, A. E., Trager, W. E, and Nelson, S. D., Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chem. Res. Toxicol., 11, 295-301 (1998) https://doi.org/10.1021/tx9701687
  31. Cho, M. K., Kim, Y. G., Lee, M. G., and Kim, S. G., Suppression of rat hepatic cytochrome P450s by protein-calorie malnutrition: Complete or partial restoration by cysteine or methionine supplementation. Arch. Biachem. Biaphys., 372, 150-158 (1999) https://doi.org/10.1006/abbi.1999.1482
  32. Cho, M. K., Kim, Y. G., Lee, M. G., and Kim, S. G., The effect of cysteine on the altered expression of class a and 11 glutathione S-transferase genes in the rat liver during proteincalorie malnutrition. Biochem. Biahys. Acta., 1502, 235-245(2000) https://doi.org/10.1016/S0925-4439(00)00046-6
  33. Cho, M. K., Kim, Y. G., Lee, M. G., and Kim, S. G., Prevention of c-Jun/activator protein-1 activation and microsomal epoxide hydrolase induction in the rat liver by cysteine during proteincalorie malnutrition. Biachem. Pharmacol., 61, 15-24 (2001) https://doi.org/10.1016/S0006-2952(00)00518-9
  34. Choi, Y. M., Kim, S. H., and Lee, M. G., Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics and pharm-acodynamics of furosemide in rats. J. Pharm. Sci., 80, 638-642 (1991a) https://doi.org/10.1002/jps.2600800705
  35. Choi, Y. M., Lee, S. H., Jang, S. H., and Lee, M. G., Effects of phenobarbital and 3-methylcholanthrene pretreatment on the pharmacokinetics and the pharmacodynamics of bumetanide in rats. Biopharm. Drug Dispos., 12, 311-324 (1991b) https://doi.org/10.1002/bdd.2510120408
  36. Chung, H. C., Sung, S. H., Kim, J. S., Kim, Y. C., and Kim, S. G., Lack of cytochrome P450 2E1 (CYP2E1) induction in the rat liver by starvation without coprophagy. Drug Metab. Dispos., 29, 213-216 (2001)
  37. Conney, A. H. and Burns, J. J., Physiological disposition and metabolic fate of chlorzoxazone (Paraflex) in man. J. Pharmacol. Exp. Ther., 128, 340-343 (1960)
  38. Cook, J. A., Smith, D. E., Cornish, L. A., Tankanow, R. M., Nicklas, J. M., and Hyneck, M. L., Kinetics, dynamics, and bioavailability of bumetanide in healthy subjects and patients with congestive heart failure. Clin. Pharmacol. Ther., 44, 487-500 (1988) https://doi.org/10.1038/clpt.1988.186
  39. Correia, M. A. and Appendix, B., Rat and human liver cytochromes P450. Substrate and inhibitor specificities and functional markers, In cytochrome P450. Structure, Mechanism, and Biochemistry (2nd edn), Oritz de Montellano PR (ed.) Pleum Press; New York and London 607-630 (1995)
  40. Crom, W. R. and Evans, W. E., Chapter 29. Methotrexate, in Applied pharmacokinetics. Principles of therapeutic drug monitoring. 2nd ed. Evans, W. E., Schontag, J. J., Jusko, W. J., (ed). Applied therapeutics, Vancouver, WA, pp. 29-1-2942 (1992)
  41. Cusack, B. J., Young, S. P, Loseke, V. L., Hurty, M. R., Beals, L., and Olson, R. D., Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit. Cancer Chemather. Pharmacol., 30, 145-148 (1992)
  42. Cuttle, L., Munns, A. J., Hogg, N. A., Scott, J. R., Hooper, W. D., Dickinson, R. G., and Gillam, EM., Phenytoin metabolism by human cytochrome P450: Involvement of P450 3A and 2C forms in secondary metabolism and drug-protein adduct formation. Drug Metab. Dispos., 28, 945-950 (2000)
  43. Davis, L. E., Lenkinski, R. E, Shinkwin, M. A., Kressel, H. Y., and Daly, J. M., The effect of dietary protein depletion on hepatic 5-fluorouracil metabolism. Cancer, 72, 3715-3722 (1993) https://doi.org/10.1002/1097-0142(19931215)72:12<3715::AID-CNCR2820721225>3.0.CO;2-W
  44. Denke, M. and Wilson, J. D., Protein and energy malnutrition. In: Principles of internal medicine Fauci AS, Braunwald E, Isselbacher KJ, Wilson JD, Martin JB, Kasper DL, Hauser SL, Longo DL, (ed). 14th ed. New York: McGraw-Hill. 452-454 (1998)
  45. Dodson, W. E. and Rust, R. S., Phenobarbital: Absorption, distribution, and excretion. In: Antiepileptic drugs. Levy RH, Mattson RH, Meldrum BS, (ed). 4th ed. New York: Raven Press, pp. 379-387 (1995)
  46. Eriksson, M., Paalzow, L., Bolme, P., and Mariam, T. W., Chloramphenicol pharmacokinetics in Ethiopian children of differing nutritional status. Eur. J. Clin. Pharmacol., 24, 819-823 (1983) https://doi.org/10.1007/BF00607094
  47. Forman, W. B., Davidson, E. D., and Webster, L. T Jr., Enzymatic conversion of salicylate to salicylurate. Mol. Pharmacol., 7, 247-259 (1971)
  48. Friedel, H. A. and Buckley, M. M., Torasemide. A review of its pharmacological properties and therapeutic potential. Drugs, 41, 81-103 (1991) https://doi.org/10.2165/00003495-199141010-00008
  49. Galinsky, R. E and Levy, G., Dose- and time-dependent elimination of acetaminophen in rats: Pharmacokinetic implications of cosubstrate depletion. J. Pharmacol. Exp. Ther., 219,14-20 (1981)
  50. Giancarlo, G. M., Venkatakrishnan, K., Granda, B. W., von Moltke, L. L., and Greenblatt, D. J., Relative contributions of CYP2C9 and 2C19 to phenytoin 4-hydroxylation in vitro: Inhibition by sulfaphenazole, omeprazole, and ticlopidine. Eur. J. Clin. Pharmacol., 57, 31-36 (2001) https://doi.org/10.1007/s002280100268
  51. Greenblatt, D. J., Clinical pharmacokinetics of oxazepam and lorazepam. Clin. Pharmacokinet., 6, 89-105 (1981) https://doi.org/10.2165/00003088-198106020-00001
  52. Greenblatt, D. J., Schillings, R. T, Kyriakopoulos, A. A., Shader, R. I., Sisenwine, S. F., Knowles, J. A., and Ruelius, H. W.,Clinical pharmacokinetics of lorazepam. I. Absorption and disposition of oral $[^{14}C]$-lorazepam. Clin. Pharmacol. Ther., 20, 329-341 (1976)
  53. Greven, J. and Heidenreich, O., Renal actions of azosemide. 2. Micropuncture investigations in rats. Arzneim.-Forsch./Drug Res., 31, 350-353 (1981)
  54. Halladay, S. C., Sipes, I. G., and Carter, D. E, Diuretic effect and metabolism of bumetanide in man. Clin. Pharmacol. Ther., 22, 179-187 (1977)
  55. Halpert, J. R., Multiplicity of steroid-inducible cytochrome P-450 in rat liver microsomes. Arch. Biochem. Biophys., 263, 59-68 (1988) https://doi.org/10.1016/0003-9861(88)90613-3
  56. Han, K. S. and Lee, M. G., Effect of a new chemoprotective agent, 2-(allylthio)pyrazine, on the pharmacokinetics of intravenous theophylline in rats. Int. J. Pharm., 184, 237-242 (1999) https://doi.org/10.1016/S0378-5173(99)00111-8
  57. Hargreaves, J. A., Howald, W. N., Racha, J. K., and Levy, R. H., Identification of enzymes responsible for the metabolism of phenobarbital. In: ISSX Proceedings; 7th North American ISSX Meeting; San Diego. Bethesda, MD: International Society for the Study of Xenobiotics, p. 259 (1996)
  58. Hendricks, M. K., Van Der Bijl, P., Parkin, D. P., and Donald, P. R., Pharmacokinetics of amikacin in children with kwashiorkor. Ann. Trap. Paediatr., 15, 295-298 (1995)
  59. Heykants, J., Michiels, M., Meuldermans, W., Monbaliu, J., Lavrijsen, K.,van Peer, A., Levron, J. C., Woestenborghs, R., and Cauwenberg, G., The pharmacokinetics of itraconazole in humans: An overview, In Recent trends in the discovery, development and evaluation of antifungal agents. Promtling RA (ed). Prous Science Publishers, Barcelona, 223-229 (1987)
  60. Heykants, J., van Peer, A., van de Velde, V., van Rooy, P, Meuldermans, W., Lavrijsen, K., Woestenborghs, R., van Cutsem, J., and Cauwenbergh, G., The clinical pharma-cokinetics of itraconazole. An overview. Mycoses, 32 (Suppl. 1),67-87 (1989) https://doi.org/10.1111/j.1439-0507.1989.tb02296.x
  61. Homeida, M., Karrar, Z. A., and Roberts, C. J., Drug metab-olism in malnourished children: A study with antipyrine. Arch. Dis. Child., 54, 299-302 (1979) https://doi.org/10.1136/adc.54.4.299
  62. Ingelman-Sundberg, M., Kaur, H., Terelius, Y, Persson, J. O., and Halliwell, B., Hydroxylation of salicylate by microsomal fractions and cytochrome P-450. Lack of production of 2,3-dihydroxybenzoate unless hydroxyl radical formation is permitted. Biochem. J., 276, 753-757 (1991)
  63. Janssen Pharmaceutica and Research Foundation, Janssen One-to-One Customer Action Center, Janssen Pharmaceutica Products, LR, April, p. 1 (2001)
  64. Janus, K., Antoszek, J., and Suszycki, S., The effect of shortterm starvation or water deprivation on caffeine pharmacokinetics in calves. Res. Vet. Sci., 70, 109-113 (2001) https://doi.org/10.1053/rvsc.2000.0446
  65. Jung, D., Disposition of acetaminophen in protein-calorie malnutrition. J. Pharmacol. Exp. Ther., 232,178-182 (1985a)
  66. Jung, D., Pharmacokinetics of theophylline in protein-calorie malnutrition. Biopharm. Drug Dispos., 6, 291-299 (1985b) https://doi.org/10.1002/bdd.2510060304
  67. Jung, D. and Nanavaty, M., The effects of age and dietary protein restriction on the pharmacokinetics of theophylline in the rat. Pharmacol. Toxicol., 66, 361-366 (1990) https://doi.org/10.1111/j.1600-0773.1990.tb00763.x
  68. Jung, D., Nanavaty, M., and Prasad, P, Disposition of procainamide and N-acetylprocainamide in protein-calorie malnutrition. Drug Metab. Dispos., 13, 359-363 (1985)
  69. Jung, D., Lam, H. D., and Chu, M., Absorption and disposition kinetics of chlorothiazide in protein-calorie malnutrition. Biopharm. Drug Dispos., 11, 53-60 (1990) https://doi.org/10.1002/bdd.2510110106
  70. Kapelanski, D. P., Daly, J. M., Copeland, E. M. 3rd., and Dudrick, S. J., Doxorubicin pharmacokinetics - The Effect of protein deprivation. J. Surg. Res., 30, 331-337 (1981) https://doi.org/10.1016/0022-4804(81)90167-0
  71. Kawamura, A., Yoshida, Y., Kimura, N., Oda, H., and Kakinuma, A., Phosphorylation/dephosphorylation steps are crucial for the induction of CYP2B1 and CYP2B2 gene expression by phenobarbital. Biochem. Biophys. Res. Gommun., 264, 530-536 (1999) https://doi.org/10.1006/bbrc.1999.1544
  72. Kim, S. H. and Lee, M. G., Influence of protein and calorie malnutrition on the pharmacokinetics and pharmacodynamics of bumetanide in rats. J. Pharm. Sci., 82, 838-843 (1993) https://doi.org/10.1002/jps.2600820817
  73. Kim, E. J. and Lee, M. G., Pharmacokinetics and pharmacody-namics of intravenous torasemide in mutant nagase analbuminemic rats. Biopharm. Drug Dispos., 24, 27-35 (2003) https://doi.org/10.1002/bdd.333
  74. Kim, S. H., Choi, Y. M., and Lee, M. G., Pharmacokinetics and pharmacodynamics of furosemide in protein-calorie malnutrition. J. Pharmacokinet. Biopharm., 21, 1-17 (1993). https://doi.org/10.1007/BF01061772
  75. Kim, Y. G., Yoon, E. J., Yoon, W H., Shim, H. J., Lee, S. D., Kim, W. B., Yang, J., and Lee, M. G., Pharmacokinetics of DA-125, a new anthracycline, after intravenous administr-ation to uranyl nitrate-induced acute renal failure rats or protein-calorie malnutrition rats. Biopharm. Drug Dispos., 17, 183-195 (1996) https://doi.org/10.1002/(SICI)1099-081X(199604)17:3<183::AID-BDD955>3.0.CO;2-M
  76. Kim, N. D., Kwak, M. K., and Kim, S. G., Inhibition ofcytochrome P450 2E1 expression by 2-(allylthio)pyrazine, a potential chemoprotective agent: Hepatoprotective effects. Biochem. Pharmacol., 53, 261-269 (1997) https://doi.org/10.1016/S0006-2952(96)00647-8
  77. Kim, Y. G., Cho. M, K., Kwon, J. W., Kim, S. G., and Lee, M. G., Effects of cysteine on the pharmacokinetics of intravenous adriamycin in rats with protein-calorie malnutrition. Res. Gommun. Mol. Pathol. Pharmacol., 107, 361-376 (2000)
  78. Kim, Y. G., Cho, M. K., Kwon, J. W, Kim, S. G., Chung, S. J., Shim, C.-K., and Lee, M. G., Effects of cysteine on the pharmacokinetics of intravenous phenytoin in rats with protein-calorie malnutrition. Int. J. Pharm., 229, 45-55 (2001a) https://doi.org/10.1016/S0378-5173(01)00815-8
  79. Kim, Y. G., Cho, M. K., Kwon, J. W, Kim, S. G., Kim, S. H., and Lee, M. G., Effects of cysteine on the pharmacokinetics and pharmacodynamics of intravenous and oral azosemide in rats with protein-calorie malnutrition. Life Sci., 68, 2329-2345 (2001b) https://doi.org/10.1016/S0024-3205(01)01025-6
  80. Kim, Y. G., Cho, M. K., Kwon, J. W, Kim, S. G., Chung, S. J., Shim, C.-K., and Lee, M. G. Effects of cysteine on the pharmacokinetics of intravenous chlorzoxazone in rats with J. H. Lee et al. protein-calorie malnutrition. Biopharm. Drug Dispos., 23, 121-129 (2002) https://doi.org/10.1002/bdd.300
  81. Kim, Y. G., Cho, M. K., Kwon, J. W, Kim, D. H., Kim, S. G., and Lee, M. G., Effects of cysteine on the pharmacokinetics of intravenous 2-(allylthio)pyrazine, a new chemoprotective agent, in rats with protein-calorie malnutrition. Int. J. Pharm., 255, 1-11 (2003a) https://doi.org/10.1016/S0378-5173(03)00054-1
  82. Kim, E. J., Suh, O. K., and Lee, M. G., Pharmacokinetics of intravenous theophylline in mutant Nagase analbuminemic rats. Life Sci., 72, 1231-1245 (2003b) https://doi.org/10.1016/S0024-3205(02)02373-1
  83. Knauf, H. and Mutschler, E., Clinical pharmacokinetics and pharmacodynamics of torasemide. Glin. Pharmacokinet., 34, 1-24 (1998) https://doi.org/10.2165/00003088-199834010-00001
  84. Kolis, S. J., Williams, T.H., and Schwartz, M. A, Identification of the urinary metabolites of $[^{14}C]$-bumetanide in the rat and their excretion by rats and dogs. Drug Metab. Dispos., 4, 169-176 (1976)
  85. Komatsu, T., Yamazaki, H., Asahi, S., Gillam, E. M., Guengerich, F. P., Nakajima, M., and Yokoi, T., Formation of a dihydroxy metabolite of phenytoin in human liver microsomes/cytosol: Roles of cytochromes P450 2C9, 2C19, and 3A4. Drug Metab. Dispos., 28, 1361-1368 (2000)
  86. Koren, G., Clinical pharmacokinetic significance of the renal tubular secretion of drugs. Glin. Pharmacokinet., 15, 165-179 (1988) https://doi.org/10.2165/00003088-198815030-00002
  87. Krishnaswamy, K., Drug metabolism and pharmacokinetics in malnutrition. Glin. Pharmacokinet., 3, 216-240 (1978) https://doi.org/10.2165/00003088-197803030-00003
  88. Krishnaswamy, K., Ushasri, V., and Naidu, N. A., The effect of malnutrition on the pharmacokinetics of phenylbutazone. Glin. Pharmacokinet., 6, 152-159 (1981) https://doi.org/10.2165/00003088-198106020-00005
  89. Lambert, C., Larochelle, P., and du Souich, P, Effects of phenobarbital and tobacco smoking on furosemide kinetics and dynamics in normal subjects. Glin. Pharmacol. Ther., 34, 170-175 (1983) https://doi.org/10.1038/clpt.1983.148
  90. Lamp, K. C., Freeman, C. D., Klutman, N. E., and Lacy, M. K., Pharmacokinetics and pharmacodynamics of the nitroimidazole antimicrobials. Glin. Pharmacokinet., 36, 353-373 (1999) https://doi.org/10.2165/00003088-199936050-00004
  91. Lange, D., Pavao, J. H., Wu, J., and Klausner, M., Effect of a cola beverage on the bioavailability of itraconazole in the presence of $H_2$ blockers. J. Glin. Pharmacol., 37, 535-540 (1997) https://doi.org/10.1002/j.1552-4604.1997.tb04332.x
  92. Lares-Asseff, I., Cravioto, J., Santiago, P, and Perez-Ortiz, B., Pharmacokinetics of metronidazole in severely malnourished and nutritionally rehabilitated children. Glin. Pharmacol. Ther., 51, 42-50 (1992) https://doi.org/10.1038/clpt.1992.6
  93. Lares-Asseff, I., Cravioto, J., Santiago, P., and Perez-Ortiz, B., A new dosing regimen for metronidazole in malnourished children. Scand. J. Infect. Dis., 25, 115-121 (1993) https://doi.org/10.3109/00365549309169679
  94. Lee, S. H., M. S. Thesis, Seoul National University, Seoul, Korea (1991)
  95. Lee, S. H. and Lee, M. G., Pharmacokinetics and pharmacody-namics of azosemide after intravenous and oral adrninis tration to rats: Absorption from various GI segments. J. Pharmacokinet. Biopharm., 24, 551-568 (1996) https://doi.org/10.1007/BF02353480
  96. Lee, S. H. and Lee, M. G., Effect of phenobarbital, 3-methylcholanthrene, and chloramphenicol pretreatment on the pharmacokinetics and pharmacodynamics of azosemide in rats. Biopharm. Drug Dispos., 18, 371-386 (1997) https://doi.org/10.1002/(SICI)1099-081X(199707)18:5<371::AID-BDD40>3.0.CO;2-L
  97. Lee, H. J. and Lee, M. G., Effects of dexamethasone on the pharmacokinetics of adriamycin after intravenous administration to rats. Res. Commun. Mol. Pathol. Pharmacol., 105, 87-96 (1999)
  98. Lee, W. I., Yoon, W. H., Shin, W. G., Song, I. S., and Lee, M. G., Pharmacokinetics and pharmacodynamics of furosemide after direct administration into the stomach or duodenum. Biopharm. Drug Dispos., 18, 753-767 (1997) https://doi.org/10.1002/(SICI)1099-081X(199712)18:9<753::AID-BDD63>3.0.CO;2-K
  99. Lee, A. K., Kang, K. W., Kim, Y. G., Cho, M. K., Lee, M. G., Shim, C. K., Chung, S. J., and Kim, S. G., Identification of genes enhanced by protein-calorie malnutrition by differential display polymerase chain reaction (expression of fibrinogen B ${\beta}$ chain, B cell translocation gene 1 and thyroid hormone responsive protein genes). Mol. Cell. Biochem., 231, 163-171 (2002) https://doi.org/10.1023/A:1014481319278
  100. Lee, A. K., Ahn, C. Y., Kim, E. J., Kwon, J. W., Chung, S. J., Kim, S. G., Shim, C.-K., and Lee, M. G., Effects of cysteine on the pharmacokinetics of itraconazole in rats with protein-calorie malnutrition. Biopharm. Drug Dispos., 24, 63-70 (2003) https://doi.org/10.1002/bdd.337
  101. Lee, A. K., Lee, J. H., Kwon, J. W., Kim, W. B., Kim, S. G., Kim, S. H., and Lee, M. G., Pharmacokinetics of clarithromycin in rats with acute renal failure induced by uranyl nitrate. Biopharm. Drug Dispos., (2004) (in press)
  102. Lelo, A., Miners, J. O., Robson, R. A., and Birkett, D. J., Quantitative assessment of caffeine partial clearances in man. Br. J. Clin. Pharmacol., 22, 183-186 (1986) https://doi.org/10.1111/j.1365-2125.1986.tb05247.x
  103. Lessard, E, Fortin, A., Belanger, P. M., Beaune, P., Hamelin, B. A., and Turgeon, J., Role of CYP2D6 in the N-hydroxylation of procainamide. Pharmacogenetics, 7, 381-390 (1997) https://doi.org/10.1097/00008571-199710000-00007
  104. Levy, R. H., Thummel, K. E, Trager, W., F., Hansten, P., D., and Eichelbaum, M., Metabolic drug interactions. Lippincott Williams & Wilkins, a Wolters Kluwer Company, Philadelphia, Baltimore, New York, London, Buenos Aires, Hongkong, Sydney, Tokyo (2000)
  105. Lewis, D. F. V., Cytochrome P450. Structure, function and mechanism. Bristol: Talyor & Francis (1996a)
  106. Lewis, D. F. V., P450 substrate specificity and metabolism. In: Cytochromes P450. Structure, function and mechanism. Bristol: Talyor & Francis, p. 123 (1996b)
  107. Lieber, C. S., Cytochrome P-4502E1: Its physiological and pathological role. Physiol. Rev., 77, 517-544 (1997)
  108. Locniskar, A. and Greenblatt, D. J., Oxidative versus conjugative biotransformation of temazepam. Biopharm. Drug Dispos., 11, 499-506 (1990) https://doi.org/10.1002/bdd.2510110604
  109. Longo, V., Ingelman-Sundberg, M., Amato, G., Salvetti, A., and Gervasi, P. G., Effect of starvation and chlormethiazole on cytochrome P450s of rat nasal mucosa. Biochem. Pharmacol., 59, 1425-1432 (2000) https://doi.org/10.1016/S0006-2952(00)00266-5
  110. Lovless, H., Arena, E, Felsted, R. L., and Bachur, N. R., Comparative mammalian metabolism of adriamycin and daunorubicin. Cancer Res.,38, 593-598 (1978)
  111. Lucas, D., Ferrara, R., Gonzalez, E., Bodenez, P., Albores, A., Manno, M., and Berthou, F., Chlorzoxazone, a selective probe for phenotyping CYP2E1 in humans. Pharmacogenetics, 9, 377-388 (1999) https://doi.org/10.1097/00008571-199906000-00013
  112. Mehta, S., Kalsi, H. K., Jayaraman, S., and Mathur, V. S., Chloramphenicol metabolism in children with protein-calorie malnutrition. Am. J. Clin. Nutr., 28, 977-981 (1975)
  113. Mehta, S., Nain, C. K., Sharma, B., and Mathur, V. S., Metabolism of sulfadiazine in children with protein calorie malnutrition. Pharmacology, 21, 369-374 (1980) https://doi.org/10.1159/000137455
  114. Mehta, S., Nain, C. K., Sharma, B., and Mathur, V. S., Disposition of four drugs in malnourished children. Drug Nutr. Interact., 1, 205-211 (1982)
  115. Meuldermans, W., Hendrickx, J., van Peer, A., Mostmans, E., Bockx, M., Roelant, D., Woestenborghs, R., Gasparini, R., Lauwers, W., van Cutsem, J., and Heykants, J., Absorption, excretion and metabolism of itracoanzole in volunteers after a single oral dose. Clinical Research Report, R. 51211/33, Janssen Pharmaceutica, Beerse, Belgium (1986)
  116. Mihranian, M. H., Wang, Y. M., and Daly, J. M., Effects of nutritional depletion and repletion on plasma methotrexate pharmacokinetics. Cancer, 54, 2268-2271 (1984) https://doi.org/10.1002/1097-0142(19841115)54:10<2268::AID-CNCR2820541034>3.0.CO;2-2
  117. Miners, J. O., Attwood, J., and Birkett, D. J., Determinants of acetaminophen metabolism: Effect of inducers and inhibitors of drug metabolism on acetaminophen's metabolic pathways. Clin. Pharmacol. Ther., 35, 480-486 (1984) https://doi.org/10.1038/clpt.1984.64
  118. Miners, J. O., Rees, D. L. P., Valente, L., Veronese, M. E., and Birkett, D. J., Human hepatic cytochrome P450 2C9 catlayzes the rate-limiting pathway of torasemide metabolism. J. Pharmacol. Exp. Ther., 272, 1076-1081 (1995)
  119. Mirghani, R. A., Yasar, U., Zheng, T., Cook, J. M., Gustafsson, L. L., Tybring, G., and Ericsson, O., Enzyme kinetics for the formation of 3-hydroxyquinine and three new metabolites of quinine in vitro; 3-hydroxylation by CYP3A4 is indeed the major metabolic pathway. Drug Metab. Dispos., 30, 1368-1371 (2002) https://doi.org/10.1124/dmd.30.12.1368
  120. Mross, K., Maessen, P.,van der Vijgh, W. J., Gall, H., Boven, E, and Pinedo, H. M., Pharmacokinetics and metabolism of epidoxorubicin and doxorubicin in humans. J. Clin. Oncol., 6, 517-526 (1988)
  121. Narang, R. K., Mehta, S., and Mathur, V. S., Pharmacokinetic study of antipyrine in malnourished children. Am. J. Clin. Nutr., 30, 1979-1982 (1977)
  122. Nehru, B., Mehta, S., Nain, C. K., and Mathur, V. S., Disposition of sulphadiazine in young rhesus monkeys with protein calorie malnutrition. Int. J. Clin. Pharmacol. Ther. Toxicol., 26, 509-512 (1988)
  123. Neugebauer, G., Besenfelder, E., and von Mollendorff, E., Pharmacokinetics and metabolism of torasemide in man. Arzneim.-Forsch./Drug Res., 38, 164-166 (1988)
  124. Ogilvie, R I., Clinical pharmacokinetics of theophylline. Clin. Pharmacokinet., 3, 267-293 (1978) https://doi.org/10.2165/00003088-197803040-00002
  125. Ogiso, T, Iwaki, M., Tanaka, H., Kobayashi, E., Tanino, T, Sawada, A, and Uno, S., Pharmacokinetic drug interactions between ampiroxicam and sulfaphenazole in rats. Bilo. Pharm. Bull., 22, 191-196 (1999) https://doi.org/10.1248/bpb.22.191
  126. Ortiz de Montellano P. R., Cytochrome P450; Structure, mechanism, and biochemistry, 2nd ed. Plenum Press, New York and London (1995)
  127. O'Shea, D., Davis, S. N., Kim, R. B., and Wilkinson, G. R, Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: A putative probe of CYP2E1 activity. Clin. Pharmacol. Ther., 56, 359-367 (1994) https://doi.org/10.1038/clpt.1994.150
  128. Otterness, D. M., Keith, R. A., Kerremans, A. L., and Weinshilboum, R. M., Mouse liver thiol methyltransferase. Assay conditions, biochemical properties, and strain variation. Drug Metab. Dispos., 14, 680-688 (1986)
  129. Ouellet, D., Hsu, A, Granneman, G. R, Carlson, G., Cavanaugh, J., Guenther, H., and Leonard, J. M., Pharmacokinetic interaction between ritonavir and clarithromycin. Clin. Pharmacol. Ther., 64, 355-362 (1998) https://doi.org/10.1016/S0009-9236(98)90065-0
  130. Pantuck, E. J., Pantuck, C. B., Weissman, C., Gil, K. M., and Askanazi, J., Stimulation of oxidative drug metabolism by parenteral refeeding of nutritionally depleted patients. Gastroenterology, 89, 241-245 (1985)
  131. Patten, C. J., Thomas, P. E., Guy, R. L., Lee, M., Gonzalez, F. J., Guengerich, F. P., and Yang, C. S., Cytochrome P450 enzymes involved in acetaminophen activation by rat and human liver microsomes and their kinetics. Chem. Res. Toxicol., 6, 511-518 (1993) https://doi.org/10.1021/tx00034a019
  132. Penzak, S. R, Gubbins, P. O., Gurley, B. J., Wang, P. L., and Saccente, M., Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers. Ther. Drug Monitor., 21, 304-309 (1999) https://doi.org/10.1097/00007691-199906000-00009
  133. Peter, R, Boeker, R, Beaune, P. H., Iwasaki, M., Guengerich, F. P., and Yang, C. S., Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450 2E1. Chem. Res. Toxicol., 3, 566-573 (1990) https://doi.org/10.1021/tx00018a012
  134. Peterson, L. A, Trevor, A., and Castagnoli, N. Jr., Stereochemical studies on the cytochrome P-450 catalyzed oxidation of (S)nicotine to the (S)-nicotine delta 1'(5')-iminium species. J. Med. Chem., 30, 249-254 (1987) https://doi.org/10.1021/jm00385a004
  135. Petri, W. A Jr., Chapter 48. Drugs used in the chemotherapy of tuberculosis, Mycobacteria avium complex disease, and leprosy, In Goodman & Gilman, The Pharmacological basis of therapeutics. Hardman, J. G., Limbird, L. L., and Gilman, A G., (ed). 10th ed. Mc Graw-Hill, Medical Publishing Division, New York. P. 1275 (2001a)
  136. Petri, W. A. Jr., Chapter 45. Penicillins, cephalosponns, and other ${\beta}$-Iactam antibiotics, In Goodman & Gilman, The Pharmacological Basis of Therapeutics. Hardman, J. G., J. H. Lee et al. Limbird, L. L.,and Gilman, A. G., (ed). 10th ed. Mc Graw-Hill, Medical Publishing Division, New York. P. 1197 (2001b)
  137. Projean, D., Baune, B., Farinotti, R., Flinois, J. P., Beaune, P., Taburet, A M., and Ducharme, J., In vitro metabolism of chloroquine: Identification of CYP2C8, CYP3A4, and CYP2D6 as the main isoforms catalyzing N-desethylchloroquine formation. Drug Metab. Dispos., 31, 748-754 (2003) https://doi.org/10.1124/dmd.31.6.748
  138. Pussard, E., Barennes, H., Daouda, H., Clavier, F., Sani, A. M., Osse, M., Granic, G., and Verdier, F., Quinine disposition in globally malnourished children with cerebral malaria. Clin. Pharmacol. Ther., 65, 500-510 (1999) https://doi.org/10.1016/S0009-9236(99)70069-X
  139. Raghuram, T. C. and Krishnaswamy, K., Influence of nutritional status on plasma levels and relative bioavailability of tetracycline. Eur. J. Clin. Pharmacol., 12, 281-284 (1977) https://doi.org/10.1007/BF00607427
  140. Raghuram, T. C. and Krishnaswamy, K., Pharmacokinetics of tetracycline in nutritional edema. Chemotherapy, 28, 428-433 (1982) https://doi.org/10.1159/000238134
  141. Raghuram, T. C., Krishnaswamy, K., and Rao, K. V., Influence of dietary restriction and protein deficiency on plasma half-life and tissue distribution of tetracycline in rats. Clin. Exp. Pharmacol. Physiol., 9, 139-144 (1982) https://doi.org/10.1111/j.1440-1681.1982.tb00790.x
  142. Raj, N. S., Misra, A., Guleria, R., and Pande, J. N., Theophylline clearance in undernourished asthma patients. Indian J. Chest. Dis. Allied. Sci., 40, 175-178 (1998)
  143. Raucy, J. L., Lasker, J. M., Lieber, C. S., and Black, M., Acetaminophen activation by human liver cytochromes P450IIE1 and P4501A2. Arch. Biochem. Biophys., 271, 270-283 (1989) https://doi.org/10.1016/0003-9861(89)90278-6
  144. Rockich, K. and Blouin, R., Effect of the acute-phase response on the pharmacokinetics of chlorzoxazone and cytochrome P-450 2E1 in vitro activity in rats.. Drug Metab. Dispos., 27, 1074-1077 (1999)
  145. Rodvold, K. A, Clinical pharmacokinetics of c1arithromycin. Clin. Pharmacokinet., 37, 385-398 (1999) https://doi.org/10.2165/00003088-199937050-00003
  146. Roh, J. K., Rha, S. Y., Lee, C. I., Lee, K. H., Lee, J. J., Shim, H. J., Lee, S. D., Kim, W. B., Yang, J., Kim, S. H., and Lee, M. G., Phase I clinical trial: Pharmacokinetics of a novel anthracycline, DA-125 and metabolites. Single dose study. Int. J. Clin. Pharmacol. Ther., 36, 312-319 (1998)
  147. Ronis, M. J., Huang, J., Longo, v., Tindberg, N., Ingelman-Sundberg, M, and Badger, T M. Expression and distribution of cytochrome P450 enzymes in male rat kidney: Effects of ethanol, acetone and dietary conditions. Biochem. Pharmacol., 55, 123-129 (1998) https://doi.org/10.1016/S0006-2952(97)00381-X
  148. Salako, L. A., Sowunmi, A, and Akinbami, F. O., Pharmacokinetics of quinine in African children suffering from kwashiorkor. Br. J. Clin. Pharmacol., 28, 197-201 (1989) https://doi.org/10.1111/j.1365-2125.1989.tb05417.x
  149. Sarich, T., Kalhorn, T., Magee, S., AI-Sayegh, F., Adams, S., Slattery, J., Goldstein, J., Nelson, S., and Wright, J., The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin. Clin. Pharmacol. Ther., 62, 21-28 (1997) https://doi.org/10.1016/S0009-9236(97)90148-X
  150. Schuchmann, H. W., Rosch, W., Koch, U., Maurer, H. H., Stengl, U., and Sutschler, E, Pharmacokinetics of azosemide in patients with T-drain after cholecystectomy. Arzneim.-Forsch./Drug Res., 42, 812-814 (1992)
  151. Seifart, H. I., Donald, P. R., de Villiers, J. N., Parkin, D. P, and Jaarsveld, P P., Isoniazid elimination kinetics in children with protein-energy malnutrition treated for tuberculous meningitis with a four-component antimicrobial regimen. Ann. Trop. Paediatr., 15, 249-254 (1995)
  152. Sharma, B., Mehta, S., Nain, C. K., and Mathur, V. S., Pharmacokinetic profile of antipyrine in young rhesus monkeys (Macaca mulatta) with protein energy malnutrition. Drug Nutr. Interact., 3, 93-98 (1985)
  153. Sharma, B., Mehta, S., Nain, C. K., and Mathur, V. S., Disposition of chloramphenicol in young rhesus monkeys with protein-energy malnutrition. Drug Nutr. Interact., 4, 333-338 (1986)
  154. Shim, H. J., Lee, E. D., Yoon, E J., Lee, S. D., Kim, W B., Yang, J., and Lee, M. G., Pharmacokinetics of FT-ADM after intravenous administration of DA-125, a prodrug of FT-ADM or FT-ADM to rats. A new adriamycin analog containing fluorine. Int. J. Pharm., 103, 147-154 (1994) https://doi.org/10.1016/0378-5173(94)90095-7
  155. Siddoway, L. A, Roden, D. M., and Woosley, R. L., Clinical pharmacology of old and new antiarrhythmic drugs. Cardiovasc. Clin., 15, 199-248 (1985)
  156. Smith, P. K., The pharmacology of salicylates and related compounds. Ann. N. Y. Acad. Sci., 86, 38-63 (1960) https://doi.org/10.1111/j.1749-6632.1960.tb42789.x
  157. Smith, D. E., Lin, E T., and Benet, L. Z., Absorption and disposition of furosemide in healthy volunteers, measured with a metabolic-specific assay. Drug Metab. Dispos., 8, 337-342 (1980)
  158. Sonne, J., Dragsted, J., Loft, S., Dossing, M., and Andreasen, F., Influence of a very low calorie diet on the clearance of oxazepam and antipyrine in man. Eur. J. Clin. Pharmacol., 36, 407-409 (1989) https://doi.org/10.1007/BF00558304
  159. Spatzenegger, M., Horsmans, Y., and Verbeeck, R. K., Differential activities of CYP1A isozymes in hepatic and intestinal microsomes of control and 3-methylcholanthrene-induced rats. Pharmacol. Toxicol., 86, 71-77 (2000) https://doi.org/10.1034/j.1600-0773.2000.d01-14.x
  160. Stafstrom, C. E., Nohria, V., Loganbill, H., Nahouraii, R., Boustany, R. M., and DeLong, G. R., Erythromycin-induced carbamazepine toxicity: A continuing problem. Arch. Pediatr. Adolesc. Med., 149, 99-101 (1995) https://doi.org/10.1001/archpedi.1995.02170130101025
  161. Suh, O. K., Kim, S. H., and Lee, M. G., Pharmacokinetics and pharmacodynamics of azosemide. Biopharm. Drug Dispos., 24, 275-297 (2003) https://doi.org/10.1002/bdd.365
  162. Syed, G. B., Sharma, D. B., and Raina, R. K., Pharmacokinetics of phenobarbitone in protein energy malnutrition. Dev. Pharmacol. Ther., 9, 317-322 (1986)
  163. Szakacs, T., Veres, Z., and Vereczkey, L., Effect of phenobar-bital and spironolactone treatment on the oxidative metabolism of antipyrine by rat liver microsomes. Pol. J. Pharmacol., 53, 11-19 (2001)
  164. Tassaneeyakul, W, Mohamed, Z., Birkett, D. J., McManus, M. E, Veronese, M. E., Tukey, R. H., Quattrochi, L. C., Gonzalez, F. J., and Miners, J. O., Caffeine as a probe for human cytochromes P450: Validation using cDNAexpression, immunoinhibition and microsomal kinetic and inhibitor techniques. Pharmacogenetics, 2, 173-183 (1992) https://doi.org/10.1097/00008571-199208000-00004
  165. Tassaneeyakul, W, Birkett, D. J., McManus, M. E, Tassaneeyakul, W, Veronese, M. E., Andersson, T., Tukey, R. H., and Miners, J. O., Caffeine metabolism by human hepatic cytochromes P450: Contributions of 1A2, 2E1 and 3A isoforms. Biochem. Pharmacol., 47, 1767-1776 (1994) https://doi.org/10.1016/0006-2952(94)90304-2
  166. Thummel, K. E., Lee, C. A., Kunze, K. L., Nelson, S. D., and Slattery, J. T., Oxidation of acetaminophen to N-acetyl-paminobenzoquinone imine by human CYP3A4. Biochem. Pharmacol., 45, 1563-1569 (1993) https://doi.org/10.1016/0006-2952(93)90295-8
  167. Tomkins, D. M., Otton, S. V.. Joharchi, N., Li, N-Y, Balster, R. F., Tyndale, R. F., and Sellers, E. M., Effects of cytochrome P450 2D1 inhibition on hydrocodone metabolism and its behavioral consequences in rats. J. Pharmacol. Exp. Ther., 280, 1374-1382 (1997)
  168. Tomlinson, E. S., Lewis, D. F., Maggs, J. L., Kroemer, H. K., Park, B. K., and Back, D. J., In vitro metabolism of dexamethasone (DEX) in human liver and kidney: The involvement of CYP3A4 and CYP17 (17,20 LYASE) and molecular modelling studies. Biochem. Pharmacol., 54, 605-611 (1997a) https://doi.org/10.1016/S0006-2952(97)00166-4
  169. Tomlinson, E. S., Maggs, J. L., Park, B. K., and Back, D. J., Dexamethasone metabolism in vitro: Species differences. J. Steroid. Biochem. Mol. Biol., 62, 345-352 (1997b) https://doi.org/10.1016/S0960-0760(97)00038-1
  170. Tranvouez, J. L., Lerebours, E., Chretien, P, Fouin-Fortunet, H., and Colin, R., Hepatic antipyrine metabolism in malnourished patients: Influence of the type of malnutrition and course after nutritional rehabilitation. Am. J. Clin. Nutr., 41, 1257-1264 (1985)
  171. Treluyer, J. M., Sultan, E., Alexandre, J. A., Roux, A, Flouvat, B., and Lagardere, B., Pharmacokinetics of aspirin in African children with normal nutrition and malnutrition. Arch. Fr. Pediatr., 48, 337-341 (1991)
  172. Treluyer, J. M., Roux, A, Mugnier, C., Flouvat, B., and Lagardere, B., Metabolism of quinine in children with global malnutrition. Metabolism of quinine in children with global malnutrition. Pediatr. Res., 40, 558-563 (1996)
  173. Tsuchiya, K., Sasaki, S., and Marumo, F., Effect of azosemide on the in vitro perfused thick ascending limb of Henle's loop from the mouse. Pharmacology, 41, 195-199 (1990) https://doi.org/10.1159/000138718
  174. Tu, Y. Y., Peng, R., Chang, Z. F., and Yang, C. S., Induction of a high affinity nitrosamine demethylase in rat liver microsomes by acetone and isopropanol. Chem. Biol. Interact., 44, 247-260 (1983) https://doi.org/10.1016/0009-2797(83)90053-4
  175. Tyndale, R. F., Li, Y, Li, N.-Y, Messina, E, Miksys, S., and Sellers, E. M., Characterization of cytochrome P-450 2D1 activity in rat brain: High-affinity kinetics for dextromethorphan. Drug Metab. Dispos., 27, 924-930 (1999)
  176. Varma, D. R., Influence of dietary protein on the anti inflammatory and ulcerogenic effects and on the pharma-cokinetics of phenylbutazone in rats. J. Pharmacol. Exp. Ther., 211, 338-344 (1979)
  177. Varma, D. R., Influence of dietary protein on the disposition and metabolism of phenylbutazone in rats. Can. J. Physiol. Pharmacol., 58, 231-236 (1980a) https://doi.org/10.1139/y80-040
  178. Varma, D. R., Myocardial effects and pharmacokinetics of digoxin and ouabain in protein-deficient guinea pigs. Can. J. Physiol. Pharmacol., 58, 564-567 (1980b) https://doi.org/10.1139/y80-092
  179. Varma, D. R. and Mulay, S., Anti-inflammatory and ulcerogenic effects and pharmacokinetics of dexamethasone in protein-deficient rats. J. Pharmacol. Exp. Ther.,214, 197-202 (1980)
  180. Varma, D. R. and Yue, T. L., Influence of age, sex, pregnancy and protein-calorie malnutrition on the pharmacokinetics of salicylate in rats. Br. J. Pharmacol., 82, 241-248 (1984a) https://doi.org/10.1111/j.1476-5381.1984.tb16464.x
  181. Varma, D. R. and Yue, T. L., Influence of protein-calorie malnutrition on the pharmacokinetics, placental transfer and tissue localization of dexamethasone in rats. Br. J. Pharmacol.,83, 131-137 (1984b) https://doi.org/10.1111/j.1476-5381.1984.tb10127.x
  182. Wallace, R. J. Jr., Brown, B. A., Griffith, D. E, Girard, W., and Tanaka, K., Reduced serum levels of clarithromycin in patients treated with multidrug regimens including rifampin or. rifabutin for Mycobacterium avium-M. intracellulare infection. J. Infect. Dis., 171, 747-750 (1995) https://doi.org/10.1093/infdis/171.3.747
  183. Wilson, R. C. and Green, N. K., Pharmacokinetics of minocycline hydrochloride in clinically normal and hypoproteinemic sheep. Am. J. Vet. Res., 47, 650-652 (1986)
  184. Woodward, B. and Filteau, S. M., Immunoenhancement in wasting protein-energy malnutrition: Assessment of present information and proposal of a new concept. Adv. Nutr. Res., 8, 11-34 (1990)
  185. Wrighton, S. A, Maurel, P., Schuetz, E. G., Watkins, P. B., Young, B., and Guzelian, P. S., Identification of the cytochrome P-450 induced by macrolide antibiotics in rat livers as the glucocorticoid responsive cytochrome P450p. Biochemistry, J. H. Lee et al. 24, 2171-2178 (1985) https://doi.org/10.1021/bi00330a010
  186. Wykes, L. J., Fiorotto, M., Burrin, D. G., Rosario, M. D., Frazer, M. E, Pond, W. G., and Jahoor, F, Chronic low protein intakes reduce tissue protein synthesis in a pig model of protein malnutrition. J. Nutr., 126, 1481-1488 (1996)
  187. Yoon, E. J., Lee, E. D., Yoon, W. H., Shim, H. J., Lee, S. D., Kim, W. B., Yang, J., and Lee, M. G., Pharmacokinetics, tissue distribution, and biliary excretion of FT-ADM after intravenous administration of DA-125, a prodrug of FT-ADM to dogs. New adriamycin analogues containing fluorine. Int. J. Pharm., 109, 181-187 (1994) https://doi.org/10.1016/0378-5173(94)90145-7
  188. Yoon, E. J., Lee, W. I., Shim, H. J., Lee, S. D., Kim, W. B., Yang, J., and Lee, M. G., Comparison of pharmacokinetics of M1, M2, M3, and M4 after intravenous administration of DA-125 or ME2303 to mice and rats, New adriamycin analogues containing fluorine. Biapharm. Drug Dispos., 17, 373-420 (1996) https://doi.org/10.1002/(SICI)1099-081X(199607)17:5<373::AID-BDD373>3.0.CO;2-U
  189. Yu, S. Y., Chung, H. C., Kim, E. J., Kim, S. H., Lee, I., Kim, S. G., and Lee, M. G., Efeects of acute renal failure induced by uranyl nitrate on the pharmacokinetics of intravenous theophylline in rats: The role of CYP2E1 induction in 1,3-dimethyluric acid formation. J. Pharm. Pharmacol., 54, 1687-1692 (2002) https://doi.org/10.1211/002235702333
  190. Yue, T. L. and Varma, D. R., Pharmacokinetics, metabolism, and disposition of salicylate in protein-deficient rats. Drug Metab. Dispos., 10, 147-152 (1982)
  191. Zimmermann, T., Yeates, R. A., Albrecht, M., Laufun, H., and Wildfeuer, A., Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in Japanese. Int. J. Clin. Pharmacol. Res., 14, 87-93 (1994a)
  192. Zimmermann, T., Yeates, R. A., Laufun, H., Pfaff, G., and Wildeuer, A, Influence of concomitant food intake on the oral absorption of two triazole antifungal agents, itraconazole and fluconazole. Eur. J. Clin. Pharmacol., 46, 147-150 (1994b)