DOI QR코드

DOI QR Code

신생아중환자의 약동학적 다양성에 영향을 미치는 요인

Contributing Factors on Pharmacokinetic Variability in Critically Ill Neonates

  • 투고 : 2017.06.27
  • 심사 : 2017.06.28
  • 발행 : 2017.06.30

초록

Neonates have large inter-individual variability in pharmacokinetic parameters of many drugs due to developmental differences. The aim of this study was to investigate the factors affecting the pharmacokinetic parameters of drugs, which are commonly used in critically ill neonates. Factors that reflect physiologic maturation such as gestational age, postnatal age, postconceptional age, birth weight, and current body weight were correlated with pharmacokinetic parameters in neonates, especially preterm infants. Comorbidity characteristics affecting pharmacokinetics in critically ill neonates were perinatal asphyxia, hypoxic ischemic encephalopathy, patent ductus arteriosus (PDA), and renal dysfunction. Administration of indomethacin or ibuprofen in neonates with PDA was associated with the reduced clearance of renally excreted drugs such as vancomycin and amikacin. Therapeutic hypothermia and extracoporeal membrane oxygenation were influencing factors on pharmacokinetic parameters in critically ill neonates. Dosing adjustment and careful monitoring according to the factors affecting pharmacokinetic variability is required for safe and effective pharmacotherapy in neonatal intensive care unit.

키워드

참고문헌

  1. Friis-Hansen B. Water distribution in the foetus and newborn infant. Acta Peadiatr Scand Suppl 1983;305:7-11.
  2. Pai VB, Nahata MC. Drug dosing in pediatric patients. In: Murphy JE, ed. Clinical pharmacokinetics. 5th ed. Bethesda, MD: Am Soc Healthsyst Pharm; 2011:29-44.
  3. Vanpee M, Blennow M, Linne T, Herin P, Aperia A. Renal function in very low birth weight infants: normal maturity reached during early childhood. J Pediatr 1992;121:784-8. https://doi.org/10.1016/S0022-3476(05)81916-X
  4. Kearns GL. Pharmacogenetics and development: are infants and children at increased risk for adverse outcomes? Curr Opin Pediatr 1995;7:220-33. https://doi.org/10.1097/00008480-199504000-00018
  5. Taketomo CK, Hodding JH, Kraus DM. Pediatric & Neonatal Dosage Handbook, 22th ed. Hudson, OH: Lexi-Comp, 2015
  6. Morselli PL, Franco-Morselli R, Bossi L. Clinical pharmacokinetics in newborns and infants. Clin Pharmacokinet 1980;5:485-527. https://doi.org/10.2165/00003088-198005060-00001
  7. Besunder JB, Reed MD, Blumer JL. Principles of drug disposition in the neonate. A critical evaluation of the pharmacokinetic-pharmacodynamic interface. Clin Pharmacokinet 1988;14:189-216 https://doi.org/10.2165/00003088-198814040-00001
  8. Friedman CA, Parks BR, Rawson JE. Gentamicin disposition in asphyxiated newborns: relationship to mean arterial pressure and urine output. Pediatr Pharmacol (New York)1982;2:189-97.
  9. Touw DJ, Graafland O, Cranendonk A, Vermeulen RJ, van Weissenbruch MM. Clinical pharmacokinetics of phenobarbital in neonates. Eur J Pharm Sci 2000;12(2):111-6. https://doi.org/10.1016/S0928-0987(00)00145-7
  10. Donn SM, Grasela TH, Goldstein, GW. Safety of a Higher Loading Dose of Phenobarbital in the Term Newborn. Pediatrics 1985;75(6):1061-4.
  11. Heimann G, Galdtke E. Pharmacokinetics of Phenobarbital in Childhood. Eur J Clin Pharmacol 1977;12(4):305-10. https://doi.org/10.1007/BF00607431
  12. Yukawa M, Yukawa E, Suematsu F, et al. Population pharmacokinetics of phenobarbital by mixed effect modelling using routine clinical pharmacokinetic data in Japanese neonates and infants: an update. J Clin Pharm Ther 2011;36(6):704-10. https://doi.org/10.1111/j.1365-2710.2010.01220.x
  13. Marsot A, Brevaut-Malaty V, Vialet R, Boulamery A, Bruguerolle B, Simon N. Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach. Fundam Clin Pharmacol 2014;28(4):465-71. https://doi.org/10.1111/fcp.12042
  14. Lee SM, Chung JY, Lee YM, et al. Effects of cytochrome P450 (CYP)2C19 polymorphisms on pharmacokinetics of phenobarbital in neonates and infants with seizures. Arch Dis Child 2012;97(6):569-72. https://doi.org/10.1136/archdischild-2011-300538
  15. van den Broek MP, Groenendaal F, Toet MC, et al. Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: a thermopharmacological approach. Clin Pharmacokinet 2012;51(10):671-9. https://doi.org/10.1007/s40262-012-0004-y
  16. Shellhaas RA, Ng CM, Dillon CH, Barks JD, Bhatt-Mehta V. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia. Pediatr Crit Care Med 2013;14(2):194-202. https://doi.org/10.1097/PCC.0b013e31825bbbc2
  17. Filippi L, la Marca G, Cavallaro G, et al. Phenobarbital for neonatal seizures in hypoxic ischemic encephalopathy: a pharmacokinetic study during whole body hypothermia. Epilepsia 2011;52(4):794-801. https://doi.org/10.1111/j.1528-1167.2011.02978.x
  18. Pitlick W, Painter M, Pippenger C. Phenobarbital pharmaockinetics in neonates. Clin P harmacol Ther 1978;23(3):346-50. https://doi.org/10.1002/cpt1978233346
  19. Grasela TH Jr, Donn SM. Neonatal population pharmacokinetics of phenobarbital derived from routine clinical data. Dev Pharmacol Ther 1985;8(6):374-83. https://doi.org/10.1159/000457062
  20. Kim SE, Kim BH, Lee S, et al. Population pharmacokinetics of theophylline in premature Korean infants. Ther Drug Monit 2013;35(3):338-44. https://doi.org/10.1097/FTD.0b013e3182866695
  21. Fukuda T, Yukawa E, Kondo G, et al. Population pharmacokinetics of theophylline in very premature Japanese infants with apnoea. J Clin Pharm Ther 2005;30(6):591-6. https://doi.org/10.1111/j.1365-2710.2005.00689.x
  22. Jones RA, Baillie E. Dosage schedule for intravenous aminophylline in apnoea of prematurity, based on pharmacokinetic studies. Arch Dis Child 1979;54(3):190-3. https://doi.org/10.1136/adc.54.3.190
  23. Dothey CI, Tserng KY, Kaw S, King KC. Maturational changes of theophylline pharmacokinetics in preterm infants. Clin Pharmacol Ther 1989;45(5):461-8. https://doi.org/10.1038/clpt.1989.59
  24. Aranda JV, Turmen T, Sasyniuk BI. Pharmacokinetics of diuretics and methylxanthines in the neonate. Eur J Clin Pharmacol 1980;18(1):55-63. https://doi.org/10.1007/BF00561479
  25. Brazier JL, Renaud H, Ribon B, Salle BL. Plasma xanthine levels in low birth weight infants treated or not treated with theophylline. Arch Dis Child 1979;54(3):194-9. https://doi.org/10.1136/adc.54.3.194
  26. Islam SI, Ali AS, Sheikh AA, Fida NM. Pharmacokinetics of theophylline in preterm neonates during the first month of life. Saudi Med J 2004;25(4):459-65.
  27. Moore ES, Faix RG, Banagale RC, Grasela TH. The population pharmacokinetics of theophylline in neonates and young infants. J Pharmacokinet Biopharm. 1989 Feb;17(1):47-66. https://doi.org/10.1007/BF01059087
  28. Young TE, Mangum B. Neofax. 24th ed. Thomson Reuters, 2011
  29. Pacifici GM. Clinical pharmacokinetics of aminoglycosides in neonates: a review. Eur J Clin Pharmacol 2009;65:419-427. https://doi.org/10.1007/s00228-008-0599-y
  30. Olavarria F, Dolz H, Krause S, et al. Torres T, Influence of gestational age and postnatal kidney maturation on the kinetics of gentamicin. Rev Chil Pediatr 1990;61(2):86-90.
  31. An SH, Kim JY, Gwak HS. Outcomes of a new dosage regimen of amikacin based on pharmacokinetic parameters of Korean neonates. Am J Health-Syst Pharm 2014;71:122-7. https://doi.org/10.2146/ajhp130308
  32. Treluyer JM, Merle Y, Tonnelier S, et al. Nonparametric population pharmacokinetic analysis of amikacin in neonates, infants and children. Antimicrob Agents Chemother 2002; 46:1381-7. https://doi.org/10.1128/AAC.46.5.1381-1387.2002
  33. Allegaert K, Anderson BJ, Cossey V et al. Limited predictability of amikacin clearance in extreme premature neonates at birth. Br J Clin Pharmacol 2006;61:39-48. https://doi.org/10.1111/j.1365-2125.2005.02530.x
  34. Peterson PO, Wells TG, Kearns GL. Amikacin dosing in neonates: evaluation of a dosing chart based on population pharmacokinetic data. Dev Pharmacol Ther 1991;16:203-11.
  35. Nielsen EI, Sandstrom M, Honore PH, Ewald U, Friberg LE. Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modeling of a prospective study. Clin Pharmacokinet 2009;48(4):253-63. https://doi.org/10.2165/00003088-200948040-00003
  36. McDougal A, Ling EW, Levine M. Vancomycin pharmacokinetics and dosing in premature neonates. Ther Drug Monit 1995;17(4):319-26. https://doi.org/10.1097/00007691-199508000-00001
  37. Lulic-Botica M, Sheer T, Edwards D, Thomas RL, Natarajan G. Impact of small-for-gestational age (SGA) status on gentamicin pharmacokinetics in neonates. J Clin Pharmacol 2014;54(1):39-45. https://doi.org/10.1002/jcph.190
  38. Radde IC. Renal function and elimination of drugs during development. In: Radde IC, Macleod SM, eds. Pediatric pharmacology and Therapeutics. St. Louis: Mosby-Tear Book. 1993;87.
  39. deHoog M, Mouton JW, van den Anker JN. Vancomycin: pharmacokinetics and administration regimens in neonates. Clin Pharmacokinet 2004;43(7):417-40. https://doi.org/10.2165/00003088-200443070-00001
  40. James A, Koren G, Milliken J, Soldin S, Prober C. Vancomycin pharmacokinetics and dose recommendations for preterm infants. Antimicrob Agents Chemother 1987;31(1):52-4. https://doi.org/10.1128/AAC.31.1.52
  41. Jarrett RV, Marinkovich GA, Gayle EL, Bass JW. Individualized pharmacokinetic profiles to compute vancomycin dosage and dosing interval in preterm infants. Pediatr Infect Dis J 1993;12(2):156-7. https://doi.org/10.1097/00006454-199302000-00010
  42. Rodvold KA, Gentry CA, Plank GS, Kraus DM, Nickel E, Gross JR. Bayesian forecasting of serum vancomycin concentrations in neonates and infants. Ther Drug Monit 1995;17(3):239-46. https://doi.org/10.1097/00007691-199506000-00005
  43. Rhodin MM, Anderson BJ, Peters AM, et al. Human renal function maturation: a quantitative description using weight and postmenstrual age. Pediatr Nephrol 2009; 24:67-76. https://doi.org/10.1007/s00467-008-0997-5
  44. Kildoo CW, Lin LM, Gabriel MH, Folli HL, Modanlou HD. Vancomycin pharmacokinetics in infants: relationship to postconceptional age and serum creatinine. Dev Pharmacol Ther 1989;14(2):77-83.
  45. Grimsley C, Thomson AH. Pharmacokinetics and dose requirements of vancomycin in neonates. Arch Dis Child Fetal Neonatal Ed 1999;81(3):F221-7. https://doi.org/10.1136/fn.81.3.F221
  46. Capparelli EV, Lane JR, Romanowski GL, et al. The influences of renal function and maturation on vancomycin elimination in newborns and infants. J Clin Pharmacol 2001;41(9):927-34. https://doi.org/10.1177/00912700122010898
  47. Frymoyer A, Meng L, Bonifacio SL, Verotta D, Guglielmo BJ. Gentamicin pharmacokinetics and dosing in neonates with hypoxic ischemic encephalopathy receiving hypothermia. Pharmacotherapy 2013; 33(7):718-26. https://doi.org/10.1002/phar.1263
  48. Gilman JT, Gal P, Levine RS, Hersh CB, Erkain NV. Factors influencing theophylline disposition in 179 newborns. Ther Drug Monit 1986;8(1):4-10. https://doi.org/10.1097/00007691-198603000-00002
  49. Gal P, Toback J, Erkan NV, Boer HR. The influence of asphyxia on phenobarbital dosing requirements in neonates. Dev Pharmacol Ther 1984;7(3):145-52. https://doi.org/10.1159/000457157
  50. Gal P, Boer HR, Toback J, Wells TJ, Erkan NV. Effect of asphyxia on theophylline clearance in newborns. South Med J 1982;75(7):836-8. https://doi.org/10.1097/00007611-198207000-00017
  51. Friedman CA, Parks BR, Rawson JE. Gentamicin disposition in asphyxiated newborns: relationship to mean arterial blood pressure and urine output. Pediatr Pharmacol (New York) 1982;2(3):189-97.
  52. Zanelli S, Buck M, Fairchild K. Physiologic and pharmacologic considerations for hypothermia therapy in neonates. J Perinatol 2011; 31(6):377-86. https://doi.org/10.1038/jp.2010.146
  53. Van den Broek MPH, Groenendaal F, Egberts ACG, et al. Effects of hypothermia on pharmacokinetics and pharmacodynamics. Clin Pharmacokin 2010; 49:277-94. https://doi.org/10.2165/11319360-000000000-00000
  54. Mark LF, Solomon A, Northington FJ, Lee CK. Gentamicin pharmacokinetics in neonates undergoing therapeutic hypothermia. Ther Drug Monit 2013;35:217-22. https://doi.org/10.1097/FTD.0b013e3182834335
  55. Ting JY, Kwan E, McDougal A, Osiovich H. Pharmacokinetics of gentamicin in newborns with moderate-to-severe hypoxicischemic encephalopathy undergoing therapeutic hypothermia. Ind J Pediatr 2015;82:119-25. https://doi.org/10.1007/s12098-014-1527-z
  56. Frymoyer A, Bonifacio SL, Drover DR, et al. Decreased Morphine Clearance in Neonates With Hypoxic Ischemic Encephalopathy Receiving Hypothermia. J Clin Pharmacol 2017;57(1):64-76. https://doi.org/10.1002/jcph.775
  57. Cies JJ, Fugarolas KN, Moore WS, Mason RW, Menkiti OR. Population Pharmacokinetics and Pharmacodynamic Target Attainment of Ampicillin in Neonates with Hypoxemic-Ischemic Encephalopathy in the Setting of Controlled Hypothermia. Pharmacotherapy 2017;37(4):456-63. https://doi.org/10.1002/phar.1916
  58. Bartlett RH, Gazzaniga AB, Toomasian J, Coran AG, Roloff D, Rucker R. Extracorporeal membrane oxygenation (ECMO) in neonatal respiratory failure. 100 cases. Ann Surg 1986;204(3):236-45. https://doi.org/10.1097/00000658-198609000-00003
  59. Buck ML. Pharmacokinetic changes during extracorporeal membrane oxygenation; Implications for drug therapy of neonates. Clin Pharmacokinet 2003;42(5):403-17. https://doi.org/10.2165/00003088-200342050-00001
  60. Marasco SF, Lukas G, McDonald M, McMillan J, Ihle B. Review of ECMO (extra corporeal membrane oxygenation) support in critically ill adult patients. Heart Lung Circ 2008;17(Suppl 4):S41-7.
  61. Lawson G, Mulla H, Upton DR, Firmin RK. Drug disposition during extracorporeal membrane oxygenation (ECMO). Paediatric Perinatal Drug Ther 2001;4:109-20.
  62. Cohen P, Collart L, Prober CG, Fischer AF, Blaschke TF. Gentamicin pharmacokinetics in neonates undergoing extracorporeal membrane oxygenation. Pediatr Infect Dis J 1990;9(8):562-6. https://doi.org/10.1097/00006454-199008000-00007
  63. Dodge WF, JelliffeRW, Zwischenberger JB, Bellanger RA, Hokanson JA, Snodgrass WR. Population pharmacokinetic models: effect of explicit versus assumed constant serum concentration assay error patterns upon parameter values of gentamicin in infants on and off extracorporeal membrane oxygenation. Ther Drug Monit 1994;16(6):552-9. https://doi.org/10.1097/00007691-199412000-00004
  64. Amaker RD, DiPiro JT, Bhatia J. Pharmacokinetics of vancomycin in critically ill infants undergoing extracorporeal membrane oxygenation. Antimicrob Agents Chemother 1996;40:1139-42.
  65. Buck ML. Vancomycin pharmacokinetics in neonates receiving extracorporeal membrane oxygenation. Pharmacotherapy 1998;18(5):1082-6.
  66. Geiduschek JM, Lynn AM, Bratton SL, et al. Morphine pharmacokinetics during continuous infusion of morphine sulfate for infants receiving extracorporeal membrane oxygenation. Crit Care Med 1997;25:360-4. https://doi.org/10.1097/00003246-199702000-00027
  67. Peters JW, Anderson BJ, Simons SH, Uges DR, Tibboel D. Morphine pharmacokinetics during venoarterial extracorporeal membrane oxygenation in neonates. Intensive Care Med 2005;31:257-63. https://doi.org/10.1007/s00134-004-2545-5
  68. Ahsman MJ, Hanekamp M, Wildschut ED, Tibboel D, Mathot RA. Population pharmacokinetics of midazolam and its metabolites during venoarterial extracorporeal membrane oxygenation in neonates. Clin Pharmacokinet 2010;49:407-19. https://doi.org/10.2165/11319970-000000000-00000
  69. Ahsman MJ, Wildschut ED, Tibboel D, Mathot RA. Pharmacokinetics of cefotaxime and desacetylcefotaxime in infants during extracorporeal membrane oxygenation. Antimicrob Agents Chemother 2010; 54:1734-41. https://doi.org/10.1128/AAC.01696-09
  70. Wildschut ED, Ahsman MJ, Houmes RJ, et al. Pharmacotherapy in neonatal and pediatric extracorporeal membrane oxygenation (ECMO). Curr Drug Metab 2012;13:767-77. https://doi.org/10.2174/138920012800840383
  71. Williams BS, Ransom JL, Gap P, et al. Gentamicin pharmacokinetics in neonates with patent ductus arteriosus. Crit Care Med 1997;25:273-275. https://doi.org/10.1097/00003246-199702000-00013
  72. Watterberg KL, Kelly HW, Johnson JD, Aldrich M, Angelus P. Effect of patent ductus arteriosus on gentamicin pharmacokinetics in very low birth weight (less than 1,500 g) babies. Dev Pharmacol Ther 1987;10(2):107-17. https://doi.org/10.1159/000457735
  73. Gal P, Ransom JL, Weaver RL. Gentamicin in neonates: the need for loading dose. Am J Perinatol 1990;7:254-7. https://doi.org/10.1055/s-2007-999494
  74. Touw DJ, Proost JH, Stevens R, Lafeber HN, van Weissenbruch MM. Gentamicin pharmacokinetics in preterm infants with a patent and a closed ductus arteriosus. Pharm World Sci 2001;23(5):200-4. https://doi.org/10.1023/A:1012490704731
  75. Zarfin Y, Koren G, Maresky D, Perlman M, MacLeod S. Possible indomethacin-aminoglycoside interaction in preterm infants. J Pediatr 1985;106(3):511-3. https://doi.org/10.1016/S0022-3476(85)80693-4
  76. Allegaert K. The impact of ibuprofen or indomethacin on renal drug clearance in neonates. J Matern Fetal Neonatal Med 2009;22(Suppl 3):88-91. https://doi.org/10.1080/14767050903180965
  77. Matic M, Norman E, Rane A, et al. Effect of UGT2B7 -900G>A (-842G>A; rs7438135) on morphine glucuronidation in preterm newborns: results from a pilot cohort. Pharmacogenomics 2014;15(12):1589-97. https://doi.org/10.2217/pgs.14.115

피인용 문헌

  1. 신생아중환자의 안전한 약물사용을 위한 약료서비스 vol.30, pp.3, 2017, https://doi.org/10.24304/kjcp.2020.30.3.143