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.
Anderson
P L
PL
Department of Experimental and Clinical Pharmacology, University of Minnesota Academic Health Sciences Center, Minneapolis, USA.
Noormohamed
S E
SE
Henry
K
K
Brundage
R C
RC
Balfour
H H
HH
Fletcher
C V
CV
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