Disposition of amodiaquine and desethylamodiaquine in HIV-infected Nigerian subjects on nevirapine-containing antiretroviral therapy.
OBJECTIVE
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.
Division of Infectious Diseases and Center for Global Health, Northwestern University, Chicago, IL, USA.
Kimberly K
KK
Scarsi
Fatai A
FA
Fehintola
Qing
Q
Ma
Francesca T
FT
Aweeka
Kristin M
KM
Darin
Gene D
GD
Morse
Ibrahim Temitope
IT
Akinola
Waheed A
WA
Adedeji
Niklas
N
Lindegardh
Joel
J
Tarning
Oladosu
O
Ojengbede
Isaac F
IF
Adewole
Babafemi
B
Taiwo
Robert L
RL
Murphy
Olusegun O
OO
Akinyinka
Sunil
S
Parikh
D000293:Adolescent; D000328:Adult; D000655:Amodiaquine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D000962:Antimalarials / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D037621:Artemisinins / Q000493:pharmacokinetics / Q000627:therapeutic use; D000077332:Artesunate; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008288:Malaria / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000627:therapeutic use*; D009549:Nigeria; D010949:Plasma / Q000737:chemistry; D055815:Young Adult; D015215:Zidovudine / Q000627:therapeutic use
D044966:Anti-Retroviral Agents; D000962:Antimalarials; D037621:Artemisinins; D000655:Amodiaquine; D019259:Lamivudine; D015215:Zidovudine; D000077332:Artesunate; D019829:Nevirapine
antimalarial; drug-drug interactions; pharmacokinetics