Semen and serum pharmacokinetics of zidovudine and zidovudine-glucuronide in men with HIV-1 infection.
OBJECTIVE
To characterize the concentration-time profiles of zidovudine and zidovudine-glucuronide in semen and serum of men infected with the human immunodeficiency-1 virus (HIV-1).


METHODS
Open-label observational study.


METHODS
University-affiliated teaching hospital and research center.


METHODS
Four asymptomatic HIV-1-infected men.


METHODS
Zidovudine administration was followed by an 8-hour intensive pharmacokinetic study on day 1. Over the next 8 days, a dose administration and timed single-sample strategy was employed to determine serum and semen concentration time profiles simultaneously.


RESULTS
Zidovudine and zidovudine-glucuronide concentrations were uniformly higher in semen than in serum except at 1 hour after the dose. The median area under the curve ratio (semen AUC0-48:serum AUC0-infinity) was 3.31 for zidovudine and 15.04 for zidovudine-glucuronide.


CONCLUSIONS
Zidovudine and zidovudine-glucuronide reach high levels in seminal plasma relative to serum. The virologic, pharmacodynamic, and public health implications of distribution to this compartment require further study.
Department of Experimental and Clinical Pharmacology, University of Minnesota Academic Health Sciences Center, Minneapolis, USA.
P L
PL
Anderson
S E
SE
Noormohamed
K
K
Henry
R C
RC
Brundage
H H
HH
Balfour
C V
CV
Fletcher
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D020719:Glucuronides / Q000097:blood / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D008297:Male; D012661:Semen / Q000378:metabolism*; D015215:Zidovudine / Q000097:blood / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D020719:Glucuronides; D015215:Zidovudine