Study of male genital tract (MGT) pharmacology is relevant to the treatment of prostatitis, prostate cancer, infertility, and seminal human immunodeficiency virus transmission. However, the time course of drug concentrations in the MGT is largely unknown. To determine the feasibility of frequent semen sampling in assessing the pharmacokinetics of the MGT, we administered efavirenz, indinavir, and zidovudine to subjects to achieve steady-state levels and then collected semen samples at sequentially decreasing ejaculation intervals. The volume of seminal plasma decreased from 4.0 (1.2-5.1) ml (median with range) at 48 h after the baseline ejaculation to 0.72 (0.45-1.6) ml 1 h after a previous ejaculation, which was still adequate for drug concentration assessment. The seminal fructose concentration also decreased. However, the concentration of prostate-specific antigen and all three drugs did not decrease, even if the ejaculation intervals decreased to 1 h. Thus, semi-intensive semen sampling can be used to assess MGT pharmacokinetics.
The study of antiretroviral drugs in semen is of interest in understanding the relationship between drug concentration and HIV transmission/resistance risk. The ability to sample semen more frequently than the traditional 48–72 hr interval would greatly facilitate these PK studies. We studied the effect of sampling interval on semen drug concentration. Six healthy subjects received continuous IV infusions of zidovudine (ZDV) to maintain steady state and exclude blood concentration as an experimental variable. ZDV concentration was measured in paired semen and blood samples collected at diminishing time intervals (48, 24, 12, 8, 4, 2, 1 hrs) over a 5 day period. We also measured seminal volume, PSA, fructose, and sperm counts in semen. All parameters were tested for changes related to sampling interval. All but 1 subject submitted all 7 paired semen and blood samples. Zidovudine S:B ratios were not significantly different (p = 0.60) across sampling time intervals, but were highly variable, ranging from 1.33 to 20.7 (median 3.4). Semen volume and fructose concentration significantly decreased (p=0.003 and 0.001, respectively) at sampling intervals < 4 hrs. PSA and sperm counts did not change with sampling interval. We have shown that 1 hour sampling intervals are feasible. ZDV S:B ratios, while not affected by 1 hour sampling intervals, were so variable as to limit our ability to detect small changes. Fructose, a seminal vesicle marker, is decreased by sampling this frequently. Clinical Pharmacology & Therapeutics (2004) 75, P15–P15; doi:
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