Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection

Michael A. Polis, Stephen C. Piscitelli, Susan Vogel, Frank G. Witebsky, Patricia S. Conville, Brent Gray Petty, Joseph A. Kovacs, Richard T. Davey, Robert E. Walker, Judith Falloon, Julia A. Metcalf, Carl Craft, H. Clifford Lane, Henry Masur

Research output: Contribution to journalArticle

Abstract

The use of antiretroviral agents and drugs for the treatment and prophylaxis of opportunistic infections has lengthened the survival of persons with AIDS. In the era of multidrug therapy, drug interactions are important considerations in designing effective and tolerable regimens. Clarithromycin has had a significant impact on the treatment of disseminated Mycobacterium avium complex infection, and zidovudine is the best-studied and one of the most widely used antiretroviral agents in this population. We conducted a study to determine the maximally tolerated dose of clarithromycin and the pharmacokinetics of clarithromycin and zidovudine individually and in combination. Mixing studies were conducted to simulate potential interaction in the gastric environment. The simultaneous administration of zidovudine and clarithromycin had little impact on the pharmacokinetics of clarithromycin or of its major metabolite. However, coadministration of zidovudine and clarithromycin at three doses (500 mg orally [p.o.] twice daily [b.i.d.], 1,000 mg p.o.b.i.d., and 2,000 mg p.o. b.i.d.) reduced the maximum concentration of zidovudine by 41% (P <0.005 and the area under the concentration-time curve from 0 to 4 h for zidovudine by 25% (P <0.05) and increased the time to maximum concentration of zidovudine by 84% (P <0.05), compared with zidovudine administered alone. Mixing studies did not detect the formation of insoluble complexes due to chelation, suggesting that the decrease in zidovudine concentrations results from some other mechanism. Simultaneous administration of zidovudine and clarithromycin appears to decrease the levels of zidovudine in serum, and it may be advisable that these drugs not be given at the same time. Drug interactions should be carefully evaluated in persons with advanced human immunodeficiency virus infection who are receiving multiple pharmacologic agents.

Original languageEnglish (US)
Pages (from-to)1709-1714
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume41
Issue number8
StatePublished - Aug 1997

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Clarithromycin
Zidovudine
Virus Diseases
HIV
Anti-Retroviral Agents
Drug Interactions
Pharmacokinetics
Mycobacterium avium Complex
Maximum Tolerated Dose
Opportunistic Infections
Pharmaceutical Preparations
Stomach
Acquired Immunodeficiency Syndrome

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Polis, M. A., Piscitelli, S. C., Vogel, S., Witebsky, F. G., Conville, P. S., Petty, B. G., ... Masur, H. (1997). Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection. Antimicrobial Agents and Chemotherapy, 41(8), 1709-1714.

Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection. / Polis, Michael A.; Piscitelli, Stephen C.; Vogel, Susan; Witebsky, Frank G.; Conville, Patricia S.; Petty, Brent Gray; Kovacs, Joseph A.; Davey, Richard T.; Walker, Robert E.; Falloon, Judith; Metcalf, Julia A.; Craft, Carl; Lane, H. Clifford; Masur, Henry.

In: Antimicrobial Agents and Chemotherapy, Vol. 41, No. 8, 08.1997, p. 1709-1714.

Research output: Contribution to journalArticle

Polis, MA, Piscitelli, SC, Vogel, S, Witebsky, FG, Conville, PS, Petty, BG, Kovacs, JA, Davey, RT, Walker, RE, Falloon, J, Metcalf, JA, Craft, C, Lane, HC & Masur, H 1997, 'Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection', Antimicrobial Agents and Chemotherapy, vol. 41, no. 8, pp. 1709-1714.
Polis, Michael A. ; Piscitelli, Stephen C. ; Vogel, Susan ; Witebsky, Frank G. ; Conville, Patricia S. ; Petty, Brent Gray ; Kovacs, Joseph A. ; Davey, Richard T. ; Walker, Robert E. ; Falloon, Judith ; Metcalf, Julia A. ; Craft, Carl ; Lane, H. Clifford ; Masur, Henry. / Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection. In: Antimicrobial Agents and Chemotherapy. 1997 ; Vol. 41, No. 8. pp. 1709-1714.
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