Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy.

Abstract

OBJECTIVES:

Artesunate plus amodiaquine is used for malaria treatment in regions with overlapping HIV endemicity. Co-administration of artesunate/amodiaquine with antiretroviral therapy (ART) may result in drug-drug interactions, but minimal data exist. This study evaluated the impact of nevirapine-based ART, containing a backbone of zidovudine and lamivudine, on the disposition of amodiaquine and its active metabolite, desethylamodiaquine (DEAQ).

METHODS:

This was an open-label, parallel-group pharmacokinetic comparison between HIV-infected, adult subjects receiving steady-state nevirapine-based ART (n = 10) and ART-naive subjects (control group, n = 11). All subjects received a loose formulation of artesunate/amodiaquine (200/600 mg) daily for 3 days, with serial pharmacokinetic sampling over 96 h following the final dose of artesunate/amodiaquine. Amodiaquine and DEAQ were quantified using a validated HPLC method with UV detection. Pharmacokinetic parameters were determined using standard non-compartmental methods.

RESULTS:

Exposures to both amodiaquine and DEAQ were significantly lower in the nevirapine-based ART group compared with the control group (amodiaquine AUC₀₋₂₄ 145 versus 204 ng·h/mL, P = 0.02; DEAQ AUC₀₋₉₆ 14,571 versus 21,648 ng·h/mL, P < 0.01). The AUCDEAQ/AUC(amodiaquine) ratio was not different between groups (ART group 116 versus control group 102, P = 0.67).

CONCLUSIONS:

Subjects on nevirapine-based ART had lower exposure to both amodiaquine and DEAQ (28.9% and 32.7%, respectively). Consequently, this may negatively impact the effectiveness of artesunate/amodiaquine in HIV-infected individuals on this ART combination.

• Authors: Kimberly K Scarsi, Fatai A Fehintola, Qing Ma, Francesca T Aweeka, Kristin M Darin, Gene D Morse, Ibrahim Temitope Akinola, Waheed A Adedeji, Niklas Lindegardh, Joel Tarning, Oladosu Ojengbede, Isaac F Adewole, Babafemi Taiwo, Robert L Murphy, Olusegun O Akinyinka, Sunil Parikh
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 5 Pg. 1370-6 (May 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 24446424 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Anti-Retroviral Agents
• Antimalarials
• Artemisinins
• Amodiaquine
• Lamivudine
• Zidovudine
• Artesunate
• Nevirapine

Topics

• Adolescent
• Adult
• Amodiaquine (pharmacokinetics, therapeutic use)
• Anti-Retroviral Agents (therapeutic use)
• Antimalarials (pharmacokinetics, therapeutic use)
• Antiretroviral Therapy, Highly Active (methods)
• Artemisinins (pharmacokinetics, therapeutic use)
• Artesunate
• Chromatography, High Pressure Liquid
• Drug Interactions
• Female
• HIV Infections (complications, drug therapy)
• Humans
• Lamivudine (therapeutic use)
• Malaria (complications, drug therapy)
• Male
• Middle Aged
• Nevirapine (therapeutic use)
• Nigeria
• Plasma (chemistry)
• Young Adult
• Zidovudine (therapeutic use)