The pharmacokinetics of amprenavir, zidovudine, and lamivudine in the genital tracts of men infected with human immunodeficiency virus type 1 (AIDS clinical trials group study 850).
The AIDS Clinical Trials Group Study 850 (ACTG 850) evaluated the penetration of zidovudine (ZDV), lamivudine (3TC), and amprenavir (APV), given alone and in combination with the 2 nucleoside analogues, into the male genital tract, because these factors may affect human immunodeficiency virus (HIV) type 1 suppression and transmission. Nineteen men receiving APV monotherapy and 12 men receiving triple therapy donated blood plasma (BP) and seminal plasma (SP) during therapy. Paired SP and BP were used to calculate compartmental concentration ratios. APV SP concentrations were consistently lower than BP concentrations, ZDV SP concentrations approximated BP concentrations early but became greater later in the dosing interval, and 3TC SP concentrations were substantially greater than BP concentrations throughout. Observed SP concentrations plotted with population BP concentration-time curves confirmed these findings, suggesting that passive diffusion (APV), slowed elimination (ZDV), and either active accumulation and/or inhibition of elimination (3TC) are responsible for SP concentrations of these agents. The antiretroviral effect of APV monotherapy was related to APV concentrations.
Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. argoyle@email.unc.edu
Arlene S
AS
Pereira
Laura M
LM
Smeaton
John G
JG
Gerber
Edward P
EP
Acosta
Sally
S
Snyder
Susan A
SA
Fiscus
Richard R
RR
Tidwell
Roy M
RM
Gulick
Robert L
RL
Murphy
Joseph J
JJ
Eron
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005663:Furans; D005837:Genitalia, Male / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D012367:RNA, Viral / Q000097:blood; D012661:Semen / Q000737:chemistry; D018709:Statistics, Nonparametric; D013449:Sulfonamides / Q000097:blood / Q000493:pharmacokinetics*; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D002219:Carbamates; D005663:Furans; D012367:RNA, Viral; D013449:Sulfonamides; D019259:Lamivudine; D015215:Zidovudine; C095108:amprenavir