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Effect of Jaeumkanghwatang (JEKHT), a Polyherbal Formula on the Pharmacokinetics Profiles of Tamoxifen in Male SD Rats (1) - Single Oral Combination Treatment of Tamoxifen 50 mg/kg with JEKHT 100 mg/kg within 5 min -

  • Kwak, Min A (Department of Internal Medicine, College of Korean Medicine, Daegu Haany University) ;
  • Park, Soo Jin (Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University) ;
  • Park, Sung Hwan (Department of Surgery, Catholic University of Daegu School of Medicine) ;
  • Lee, Young Joon (Department of Preventive Medicine, College of Korean Medicine, Daegu Haany University) ;
  • Ku, Sae Kwang (Department of Anatomy and Histology, College of Korean Medicine, Daegu Haany University)
  • Received : 2016.02.04
  • Accepted : 2016.04.19
  • Published : 2016.06.30

Abstract

Objectives: The objective of this study was to elucidate the effect of Jaeumkanghwatang (JEKHT) on the plasma concentration and pharmacokinetics of tamoxifen in combination therapy as a process of the comprehensive and integrative medicine against breast cancer. Methods: After 50 mg/kg of tamoxifen treatment, JEKHT 100 mg/kg was orally administered within 5 min. The plasma were collected at 30 min before administration, 30min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of JEKHT treatment, and plasma concentrations of tamoxifen were analyzed using LC-MS/MS methods. PK parameters of tamoxifen ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with tamoxifen single administered rats. Results: JEKHT did not influenced on the plasma concentrations and pharmacokinetics of tamoxifen after single oral co-administration, within 5min except for some negligible effects on plasma concentration. The $T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$ of tamoxifen in co-administered rats were quite similar to those of tamoxifen single treated rats. Conclusions: Based on the results of the present study, JEKHT did not influenced on the oral bioavailability of tamoxifen, when they were single co-administered within 5min. However, more detail pharmacokinetic studies should be tested to conclude the possibilities that can be used as comprehensive and integrative therapy with JEKHT and tamoxifen for breast cancers, when they were co-administered, like the effects on the pretreatment of JEKHT and after repeat co-administrations.

Keywords

References

  1. The BIG 1-98 Collaborative Group. Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med. 2009;361(8):766-776. https://doi.org/10.1056/NEJMoa0810818
  2. Jordan VC. Fourteenth Gaddum Memorial Lecture. A current view of tamoxifen for the treatment and prevention of breast cancer. Br J Pharmacol. 1993;110(2):507-517. https://doi.org/10.1111/j.1476-5381.1993.tb13840.x
  3. Jordan VC. Tamoxifen (ICI46,474) as a targeted therapy to treat and prevent breast cancer. Br J Pharmacol. 2006;147 Suppl 1:S269-276. https://doi.org/10.1038/sj.bjp.0706507
  4. Steiner AZ, Terplan M, Paulson RJ. Comparison of tamoxifen and clomiphene citrate for ovulation induction: a meta-analysis. Hum Reprod. 2005;20(6):1511-1515. https://doi.org/10.1093/humrep/deh840
  5. van Bommel EF, Hendriksz TR, Huiskes AW, Zeegers AG. Brief communication: tamoxifen therapy for nonmalignant retroperitoneal fibrosis. Ann Intern Med. 2006;144(2):101-106. https://doi.org/10.7326/0003-4819-144-2-200601170-00007
  6. Boccardo F, Rubagotti A, Battaglia M, Di Tonno P, Selvaggi FP, Conti G, et al. Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. J Clin Oncol. 2005;23(4):808 -815. https://doi.org/10.1200/JCO.2005.12.013
  7. Fradet Y, Egerdie B, Andersen M, Tammela TL, Nachabe M, Armstrong J, et al. Tamoxifen as prophylaxis for prevention of gynaecomastia and breast pain associated with bicalutamide 150 mg monotherapy in patients with prostate cancer: a randomised, placebo-controlled, dose-response study. Eur Urol. 2007;52(1):106-114. https://doi.org/10.1016/j.eururo.2007.01.031
  8. Einat H, Yuan P, Szabo ST, Dogra S, Manji HK. Protein kinase C inhibition by tamoxifen antagonizes manic-like behavior in rats: implications for the development of novel therapeutics for bipolar disorder. Neuropsychobiology. 2007;55 (3-4):123-131. https://doi.org/10.1159/000106054
  9. Amrollahi Z, Rezaei F, Salehi B, Modabbernia AH, Maroufi A, Esfandiari GR, et al. Double-blind, randomized, placebo-controlled 6-week study on the efficacy and safety of the tamoxifen adjunctive to lithium in acute bipolar mania. J Affect Disord. 2011;129(1-3):327-331. https://doi.org/10.1016/j.jad.2010.08.015
  10. Blackwell KL, Haroon ZA, Shan S, Saito W, Broadwater G, Greenberg CS, et al. Tamoxifen inhibits angiogenesis in estrogen receptor-negative animal models. Clin Cancer Res. 2000;6(11): 4359-4364.
  11. Feil R, Brocard J, Mascrez B, LeMeur M, Metzger D, Chambon P. Ligand-activated site-specific recombination in mice. Proc Natl Acad Sci U S A. 1996;93(20):10887-10890. https://doi.org/10.1073/pnas.93.20.10887
  12. Dabelic N, Jukic T, Labar Z, Novosel SA, Matesa N, Kusic Z. Riedel's thyroiditis treated with tamoxifen. Croat Med J. 2003;44(2): 239-241.
  13. Fatourechi MM, Hay ID, McIver B, Sebo TJ, Fatourechi V. Invasive fibrous thyroiditis (Riedel thyroiditis): the Mayo Clinic experience, 1976-2008. Thyroid. 2011;21(7):765-772. https://doi.org/10.1089/thy.2010.0453
  14. Eugster EA, Shankar R, Feezle LK, Pescovitz OH. Tamoxifen treatment of progressive precocious puberty in a patient with McCune-Albright syndrome. J Pediatr Endocrinol Metab. 1999; 12(5):681-686. https://doi.org/10.1515/JPEM.1999.12.5.681
  15. Sawathiparnich P, Osuwanaratana P, Santiprabhob J, Likitmaskul S. Tamoxifen improved final height prediction in a girl with McCune-Albright syndrome: patient report and literature review. J Pediatr Endocrinol Metab. 2006;19(1):81-86. https://doi.org/10.1515/JPEM.2006.19.1.81
  16. Shang Y, Hu X, DiRenzo J, Lazar MA, Brown M. Cofactor dynamics and sufficiency in estrogen receptor-regulated transcription. Cell. 2000;103(6):843-852. https://doi.org/10.1016/S0092-8674(00)00188-4
  17. Massarweh S, Osborne CK, Creighton CJ, Qin L, Tsimelzon A, Huang S, et al. Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res. 2008;68(3):826-833. https://doi.org/10.1158/0008-5472.CAN-07-2707
  18. Hurtado A, Holmes KA, Geistlinger TR, Hutcheson IR, Nicholson RI, Brown M, et al. Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature. 2008;456(7222):663-666. https://doi.org/10.1038/nature07483
  19. Vehmanen L, Elomaa I, Blomqvist C, Saarto T. Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status. J Clin Oncol. 2006;24(4):675-680. https://doi.org/10.1200/JCO.2005.02.3515
  20. Grilli S. Tamoxifen (TAM): the dispute goes on. Ann Ist Super Sanita. 2006;42(2):170-173.
  21. Decensi A, Maisonneuve P, Rotmensz N, Bettega D, Costa A, Sacchini V, et al. Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial. Circulation. 2005;111(5):650-656. https://doi.org/10.1161/01.CIR.0000154545.84124.AC
  22. Osman KA, Osman MM, Ahmed MH. Tamoxifen-induced non-alcoholic steatohepatitis: where are we now and where are we going? Expert Opin Drug Saf. 2007;6(1):1-4. https://doi.org/10.1517/14740338.6.1.1
  23. Paganini-Hill A, Clark LJ. Preliminary assessment of cognitive function in breast cancer patients treated with tamoxifen. Breast Cancer Res Treat. 2000;64(2):165-176. https://doi.org/10.1023/A:1006426132338
  24. Eberling JL, Wu C, Tong-Turnbeaugh R, Jagust WJ. Estrogen- and tamoxifen-associated effects on brain structure and function. Neuroimage. 2004;21(1):364-371. https://doi.org/10.1016/j.neuroimage.2003.08.037
  25. Mortimer JE, Boucher L, Baty J, Knapp DL, Ryan E, Rowland JH. Effect of tamoxifen on sexual functioning in patients with breast cancer. J Clin Oncol. 1999;17(5):1488-1492. https://doi.org/10.1200/JCO.1999.17.5.1488
  26. Cella D, Fallowfield L, Barker P, Cuzick J, Locker G, Howell A, et al. Quality of life of postmenopausal women in the ATAC ("Arimidex", tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for early breast cancer. Breast Cancer Res Treat. 2006;100(3):273-284. https://doi.org/10.1007/s10549-006-9260-6
  27. Karimian E, Chagin AS, Gjerde J, Heino T, Lien EA, Ohlsson C, et al. Tamoxifen impairs both longitudinal and cortical bone growth in young male rats. J Bone Miner Res. 2008; 23(8):1267-1277. https://doi.org/10.1359/jbmr.080319
  28. Wilson SC, Knight PG, Cunningham FJ. Evidence for the involvement of central conversion of testosterone to oestradiol-17b in the regulation of luteinizing hormone secretion in the cockerel. J Endocrinol. 1983;99(2):301-310. https://doi.org/10.1677/joe.0.0990301
  29. Nalbandian G, Paharkova-Vatchkova V, Mao A, Nale S, Kovats S. The selective estrogen receptor modulators, tamoxifen and raloxifene, impair dendritic cell differentiation and activation. J Immunol. 2005;175(4):2666-2675. https://doi.org/10.4049/jimmunol.175.4.2666
  30. Berstein LM, Wang JP, Zheng H, Yue W, Conaway M, Santen RJ. Long-term exposure to tamoxifen induces hypersensitivity to estradiol. Clin Cancer Res. 2004;10(4):1530-1534. https://doi.org/10.1158/1078-0432.CCR-0433-03
  31. Rousset-Jablonski C, Thalabard JC, Gompel A. Tamoxifen contraindicated in women with hereditary angioedema? Ann Oncol. 2009;20(7): 1281-1282.
  32. Kim SY, Suzuki N, Santosh Laxmi YR, Rieger R, Shibutani S. a-hydroxylation of tamoxifen and toremifene by human and rat cytochrome P450 3A subfamily enzymes. Chem Res Toxicol. 2003;16(9):1138-1144. https://doi.org/10.1021/tx0300131
  33. Notley LM, Crewe KH, Taylor PJ, Lennard MS, Gillam EM. Characterization of the human cytochrome P450 forms involved in metabolism of tamoxifen to its a-hydroxy and a,4-dihydroxy derivatives. Chem Res Toxicol. 2005;18(10): 1611-1618. https://doi.org/10.1021/tx050140s
  34. Lien EA, Anker G, Lonning PE, Solheim E, Ueland PM. Decreased serum concentrations of tamoxifen and its metabolites induced by aminoglutethimide. Cancer Res. 1990;50(18): 5851-5857.
  35. Ritchie LD, Grant SM. Tamoxifen-warfarin interaction: the Aberdeen hospitals drug file. BMJ. 1989;298(6682):1253.
  36. Tenni P, Lalich DL, Byrne MJ. Life threatening interaction between tamoxifen and warfarin. BMJ. 1989;298(6666):93.
  37. Lamberts SW, Verleun T, Hofland L, Oosterom R. Differences in the interaction between dopamine and estradiol on prolactin release by cultured normal and tumorous human pituitary cells. J Clin Endocrinol Metab. 1986;63(6):1342-1347. https://doi.org/10.1210/jcem-63-6-1342
  38. Dowsett M, Pfister C, Johnston SR, Miles DW, Houston SJ, Verbeek JA, et al. Impact of tamoxifen on the pharmacokinetics and endocrine effects of the aromatase inhibitor letrozole in postmenopausal women with breast cancer. Clin Cancer Res. 1999;5(9):2338-2343.
  39. Reid AD, Horobin JM, Newman EL, Preece PE. Tamoxifen metabolism is altered by simultaneous administration of medroxyprogesterone acetate in breast cancer patients. Breast Cancer Res Treat. 1992;22(2):153-156. https://doi.org/10.1007/BF01833345
  40. Dehal SS, Brodie AM, Kupfer D. The aromatase inactivator 4-hydroxyandrostenedione (4-OH-A) inhibits tamoxifen metabolism by rat hepatic cytochrome P-450 3A: potential for drug-drug interaction of tamoxifen and 4-OH-A in combined anti-breast cancer therapy. Drug Metab Dispos. 1999;27(3):389-394.
  41. West CM, Reeves SJ, Brough W. Additive interaction between tamoxifen and rifampicin in human biliary tract carcinoma cells. Cancer Lett. 1990;55(2):159-163. https://doi.org/10.1016/0304-3835(90)90027-U
  42. Mani C, Gelboin HV, Park SS, Pearce R, Parkinson A, Kupfer D. Metabolism of the antimammary cancer antiestrogenic agent tamoxifen. I. Cytochrome P-450-catalyzed N-demethylation and 4-hydroxylation. Drug Metab Dispos. 1993;21(4):645-656.
  43. Mani C, Pearce R, Parkinson A, Kupfer D. Involvement of cytochrome P4503A in catalysis of tamoxifen activation and covalent binding to rat and human liver microsomes. Carcinogenesis. 1994;15(12):2715-2720. https://doi.org/10.1093/carcin/15.12.2715
  44. Williams JA, Ring BJ, Cantrell VE, Jones DR, Eckstein J, Ruterbories K, et al. Comparative metabolic capabilities of CYP3A4, CYP3A5, and CYP3A7. Drug Metab Dispos. 2002;30(8): 883-891. https://doi.org/10.1124/dmd.30.8.883
  45. Jung DY, Ha HK, Lee HY, Lee JA, Lee JK, Huang DS, et al. Stimulation of the immune response by Yin-Tonifying formula. J Korean Oriental Med. 2010;31:112-123.
  46. Sekiya N, Hikiami H, Sakai S, Kainuma M, Goto H, Shibahara N, et al. Experimental Application of Jiin-koka-to to Cases of Bronchial Asthma. Kampo Medicine. 2003;54(6):1097-1101. https://doi.org/10.3937/kampomed.54.1097
  47. Kim YK, Kim HJ, Kim WS, Park HJ, Moon G, Kim DW, et al. Inhibitory effect of Jaeumganhwa-tang on allergic inflammatory reaction. Korean J Orien Inter Med. 2004;25:174-182.
  48. Zheng H, Lee Y, Yoo H, Cho C. Case Study of a Breast Cancer Patient Accompanying with Hot Flush by Tamoxifen Whose Condition Was Improved by Jayeumganghwa-tang. Korean J Orien Inter Med. 2010;6:395-400.
  49. Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. Oxford: Taylor & Francis; 1982.
  50. Bailer AJ. Testing for the equality of area under the curves when using destructive measurement techniques. J Pharmacokinet Biopharm. 1988; 16(3):303-309. https://doi.org/10.1007/BF01062139
  51. Chiou WL. Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level-time curve. J Pharmacokinet Biopharm. 1978;6(6):539-546. https://doi.org/10.1007/BF01062108
  52. Adam HK, Gay MA, Moore RH. Measurement of tamoxifen in serum by thin--layer densitometry. J Endocrinol. 1980;84(1):35-42. https://doi.org/10.1677/joe.0.0840035
  53. Adam HK, Patterson JS, Kemp JV. Studies on the metabolism and pharmacokinetics of tamoxifen in normal volunteers. Cancer Treat Rep. 1980;64(6-7):761-764.
  54. Fabian C, Sternson L, Barnett M. Clinical pharmacology of tamoxifen in patients with breast cancer: comparison of traditional and loading dose schedules. Cancer Treat Rep. 1980;64(6-7):765-773.
  55. Jordan VC, Bain RR, Brown RR, Gosden B, Santos MA. Determination and pharmacology of a new hydroxylated metabolite of tamoxifen observed in patient sera during therapy for advanced breast cancer. Cancer Res. 1983;43(3): 1446-1450.
  56. Murphy C, Fotsis T, Pantzar P, Adlercreutz H, Martin F. Analysis of tamoxifen and its metabolites in human plasma by gas chromatography-mass spectrometry (GC-MS) using selected ion monitoring (SIM). J Steroid Biochem. 1987; 26(5):547-555. https://doi.org/10.1016/0022-4731(87)90006-9
  57. Jordan VC. Metabolites of tamoxifen in animals and man: identification, pharmacology, and significance. Breast Cancer Res Treat. 1982; 2(2):123-138. https://doi.org/10.1007/BF01806449
  58. Sun D, Sharma AK, Dellinger RW, Blevins -Primeau AS, Balliet RM, Chen G, et al. Glucuronidation of active tamoxifen metabolites by the human UDP glucuronosyltransferases. Drug Metab Dispos. 2007;35(11):2006-2014. https://doi.org/10.1124/dmd.107.017145
  59. AstraZeneca Pharaceuticals. Nolvadex (tamoxifen citrate) prescribing information. Wilmington, DE: 2003 June.
  60. Hall WA, Doolittle ND, Daman M, Bruns PK, Muldoon L, Fortin D, et al. Osmotic blood-brain barrier disruption chemotherapy for diffuse pontine gliomas. J Neurooncol. 2006; 77(3):279-284. https://doi.org/10.1007/s11060-005-9038-4

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