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. 1993 Jul;37(7):1426–1431. doi: 10.1128/aac.37.7.1426

Pharmacokinetic interaction between rifampin and zidovudine.

D M Burger 1, P L Meenhorst 1, C H Koks 1, J H Beijnen 1
PMCID: PMC187988  PMID: 8363370

Abstract

A potential pharmacokinetic interaction between rifampin (Rimactan, Rifadin) and zidovudine (AZT, Retrovir) was investigated in the population of human immunodeficiency virus-infected patients at our hospital. The results from four patients who were on long-term (> or = 6 months) combination therapy with zidovudine and rifampin are presented. In all cases of combined use of zidovudine and rifampin, a lower area under the plasma concentration-time curve (AUC) and, consequently, a higher apparent clearance of zidovudine were found, compared with a reference population of zidovudine users. Patients had a low to normal maximum concentration of zidovudine in plasma. Elimination half-lives were normal in all but one patient. Zidovudine glucuronide concentrations were determined in three patients and three control subjects. The patients all had relatively higher peak plasma concentrations and higher AUCs of zidovudine glucuronide than the control subjects. In one patient, zidovudine and zidovudine glucuronide were also measured 2.5 months after discontinuation of rifampin. The AUC of zidovudine increased by a factor of 2. These data are in agreement with an enzyme-inducing effect of rifampin on the glucuronidation of zidovudine. They indicate that long-term combination therapy of rifampin and zidovudine leads to increased clearance of zidovudine, which may have therapeutic consequences.

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Selected References

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  1. Acocella G. Clinical pharmacokinetics of rifampicin. Clin Pharmacokinet. 1978 Mar-Apr;3(2):108–127. doi: 10.2165/00003088-197803020-00002. [DOI] [PubMed] [Google Scholar]
  2. Antoniskis D., Easley A. C., Espina B. M., Davidson P. T., Barnes P. F. Combined toxicity of zidovudine and antituberculosis chemotherapy. Am Rev Respir Dis. 1992 Feb;145(2 Pt 1):430–434. doi: 10.1164/ajrccm/145.2_Pt_1.430. [DOI] [PubMed] [Google Scholar]
  3. Bennett P. N., John V. A., Whitmarsh V. B. Effect of rifampicin on metoprolol and antipyrine kinetics. Br J Clin Pharmacol. 1982 Mar;13(3):387–391. doi: 10.1111/j.1365-2125.1982.tb01390.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boucher C. A. Clinical significance of zidovudine-resistant human immunodeficiency viruses. Res Virol. 1992 Mar-Apr;143(2):134–136. doi: 10.1016/s0923-2516(06)80098-1. [DOI] [PubMed] [Google Scholar]
  5. Child S., Montaner J., Tsoukas C., Fanning M., Le T., Wall R. A., Ruedy J. Canadian multicenter azidothymidine trial: AZT pharmacokinetics. J Acquir Immune Defic Syndr. 1991;4(9):865–870. [PubMed] [Google Scholar]
  6. Collins J. M., Unadkat J. D. Clinical pharmacokinetics of zidovudine. An overview of current data. Clin Pharmacokinet. 1989 Jul;17(1):1–9. doi: 10.2165/00003088-198917010-00001. [DOI] [PubMed] [Google Scholar]
  7. Davidson P. T., Le H. Q. Drug treatment of tuberculosis--1992. Drugs. 1992 May;43(5):651–673. doi: 10.2165/00003495-199243050-00003. [DOI] [PubMed] [Google Scholar]
  8. Ellner J. J., Goldberger M. J., Parenti D. M. Mycobacterium avium infection and AIDS: a therapeutic dilemma in rapid evolution. J Infect Dis. 1991 Jun;163(6):1326–1335. doi: 10.1093/infdis/163.6.1326. [DOI] [PubMed] [Google Scholar]
  9. Haumont M., Magdalou J., Lafaurie C., Ziegler J. M., Siest G., Colin J. N. Phenobarbital inducible UDP-glucuronosyltransferase is responsible for glucuronidation of 3'-azido-3'-deoxythymidine: characterization of the enzyme in human and rat liver microsomes. Arch Biochem Biophys. 1990 Sep;281(2):264–270. doi: 10.1016/0003-9861(90)90442-2. [DOI] [PubMed] [Google Scholar]
  10. Herman R. J., Nakamura K., Wilkinson G. R., Wood A. J. Induction of propranolol metabolism by rifampicin. Br J Clin Pharmacol. 1983 Nov;16(5):565–569. doi: 10.1111/j.1365-2125.1983.tb02218.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hopewell P. C. Impact of human immunodeficiency virus infection on the epidemiology, clinical features, management, and control of tuberculosis. Clin Infect Dis. 1992 Sep;15(3):540–547. doi: 10.1093/clind/15.3.540. [DOI] [PubMed] [Google Scholar]
  12. Horsburgh C. R., Jr Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med. 1991 May 9;324(19):1332–1338. doi: 10.1056/NEJM199105093241906. [DOI] [PubMed] [Google Scholar]
  13. Kavesh N. G., Holzman R. S., Seidlin M. The combined toxicity of azidothymidine and antimycobacterial agents. A retrospective study. Am Rev Respir Dis. 1989 May;139(5):1094–1097. doi: 10.1164/ajrccm/139.5.1094. [DOI] [PubMed] [Google Scholar]
  14. Laskin O. L., de Miranda P., Blum M. R. Azidothymidine steady-state pharmacokinetics in patients with AIDS and AIDS-related complex. J Infect Dis. 1989 Apr;159(4):745–747. doi: 10.1093/infdis/159.4.745. [DOI] [PubMed] [Google Scholar]
  15. Lee B. L., Safrin S. Interactions and toxicities of drugs used in patients with AIDS. Clin Infect Dis. 1992 Mar;14(3):773–779. doi: 10.1093/clinids/14.3.773-a. [DOI] [PubMed] [Google Scholar]
  16. McLeod G. X., Hammer S. M. Zidovudine: five years later. Ann Intern Med. 1992 Sep 15;117(6):487–501. doi: 10.7326/0003-4819-117-6-487. [DOI] [PubMed] [Google Scholar]
  17. Morse G. D., Olson J., Portmore A., Taylor C., Plank C., Reichman R. C. Pharmacokinetics of orally administered zidovudine among patients with hemophilia and asymptomatic human immunodeficiency virus (HIV) infection. Antiviral Res. 1989 Mar;11(2):57–65. doi: 10.1016/0166-3542(89)90008-9. [DOI] [PubMed] [Google Scholar]
  18. Morse G. D., Portmore A. C., Marder V., Plank C., Olson J., Taylor C., Bonnez W., Reichman R. C. Intravenous and oral zidovudine pharmacokinetics and coagulation effects in asymptomatic human immunodeficiency virus-infected hemophilia patients. Antimicrob Agents Chemother. 1992 Oct;36(10):2245–2252. doi: 10.1128/aac.36.10.2245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Prescott L. F., Critchley J. A., Balali-Mood M., Pentland B. Effects of microsomal enzyme induction on paracetamol metabolism in man. Br J Clin Pharmacol. 1981 Aug;12(2):149–153. doi: 10.1111/j.1365-2125.1981.tb01193.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Singlas E., Pioger J. C., Taburet A. M., Colaneri S., Fillastre J. P. Comparative pharmacokinetics of zidovudine (AZT) and its metabolite (G.AZT) in healthy subjects and HIV seropositive patients. Eur J Clin Pharmacol. 1989;36(6):639–640. doi: 10.1007/BF00637752. [DOI] [PubMed] [Google Scholar]
  21. Stagg M. P., Cretton E. M., Kidd L., Diasio R. B., Sommadossi J. P. Clinical pharmacokinetics of 3'-azido-3'-deoxythymidine (zidovudine) and catabolites with formation of a toxic catabolite, 3'-amino-3'-deoxythymidine. Clin Pharmacol Ther. 1992 Jun;51(6):668–676. doi: 10.1038/clpt.1992.79. [DOI] [PubMed] [Google Scholar]
  22. Stretcher B. N. State-of-the-art of zidovudine monitoring. J Clin Lab Anal. 1991;5(1):60–68. doi: 10.1002/jcla.1860050112. [DOI] [PubMed] [Google Scholar]
  23. Tadepalli S. M., Puckett L., Jeal S., Kanics L., Quinn R. P. Differential assay of zidovudine and its glucuronide metabolite in serum and urine with a radioimmunoassay kit. Clin Chem. 1990 Jun;36(6):897–900. [PubMed] [Google Scholar]
  24. Unadkat J. D., Collier A. C., Crosby S. S., Cummings D., Opheim K. E., Corey L. Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal. AIDS. 1990 Mar;4(3):229–232. doi: 10.1097/00002030-199003000-00008. [DOI] [PubMed] [Google Scholar]
  25. Venkatesan K. Pharmacokinetic drug interactions with rifampicin. Clin Pharmacokinet. 1992 Jan;22(1):47–65. doi: 10.2165/00003088-199222010-00005. [DOI] [PubMed] [Google Scholar]

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