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Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2012 Sep; Vol. 67 (9), pp. 2213-21. Date of Electronic Publication: 2012 Jun 11. - Publication Year :
- 2012
-
Abstract
- Objectives: Co-administration of artemether/lumefantrine with antiretroviral therapy has potential for pharmacokinetic drug interactions. We investigated drug-drug interactions between artemether/lumefantrine and efavirenz or nevirapine.<br />Methods: We performed a cross-over study in which HIV-infected adults received standard six-dose artemether/lumefantrine 80/480 mg before and at efavirenz or nevirapine steady state. Artemether, dihydroartemisinin, lumefantrine, efavirenz and nevirapine plasma concentrations were measured and compared.<br />Results: Efavirenz significantly reduced artemether maximum concentration (C(max)) and plasma AUC (median 29 versus 12 ng/mL, P < 0.01, and 119 versus 25 ng · h/mL, P < 0.01), dihydroartemisinin C(max) and AUC (median 120 versus 26 ng/mL, P < 0.01, and 341 versus 84 ng · h/mL, P < 0.01), and lumefantrine C(max) and AUC (median 8737 versus 6331 ng/mL, P = 0.03, and 280 370 versus 124 381 ng · h/mL, P < 0.01). Nevirapine significantly reduced artemether C(max) and AUC (median 28 versus 11 ng/mL, P < 0.01, and 123 versus 34 ng · h/mL, P < 0.01) and dihydroartemisinin C(max) and AUC (median 107 versus 59 ng/mL, P < 0.01, and 364 versus 228 ng · h/mL, P < 0.01). Lumefantrine C(max) and AUC were non-significantly reduced by nevirapine. Artemether/lumefantrine reduced nevirapine C(max) and AUC (median 8620 versus 4958 ng/mL, P < 0.01, and 66 329 versus 35 728 ng · h/mL, P < 0.01), but did not affect efavirenz exposure.<br />Conclusions: Co-administration of artemether/lumefantrine with efavirenz or nevirapine resulted in a reduction in artemether, dihydroartemisinin, lumefantrine and nevirapine exposure. These drug interactions may increase the risk of malaria treatment failure and development of resistance to artemether/lumefantrine and nevirapine. Clinical data from population pharmacokinetic and pharmacodynamic trials evaluating the impact of these drug interactions are urgently needed.
- Subjects :
- Adult
Alkynes
Anti-HIV Agents administration & dosage
Antimalarials administration & dosage
Artemether, Lumefantrine Drug Combination
Artemisinins administration & dosage
Benzoxazines administration & dosage
Cross-Over Studies
Cyclopropanes
Drug Combinations
Ethanolamines administration & dosage
Female
Fluorenes administration & dosage
HIV Infections complications
HIV Infections drug therapy
Humans
Malaria complications
Malaria drug therapy
Male
Nevirapine administration & dosage
Plasma chemistry
Uganda
Anti-HIV Agents pharmacokinetics
Antimalarials pharmacokinetics
Artemisinins pharmacokinetics
Benzoxazines pharmacokinetics
Drug Interactions
Ethanolamines pharmacokinetics
Fluorenes pharmacokinetics
Nevirapine pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 67
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 22687893
- Full Text :
- https://doi.org/10.1093/jac/dks207