Abstract
The male genital tract is a complex collection of anatomically and biochemically distinct compartments that contribute to the ejaculate. Understanding the pharmacokinetics in these compartments should inform rational therapeutics involving these glands. Nineteen men were administered a single dose of 600 mg chloroquine (base) and 975 mg aspirin before providing a semen sample by masturbation with fractionation into a 5-compartment collection device. Fractions were assayed for fructose (unique seminal vesicle marker), prostate-specific antigen (unique prostate marker), salicylate, and chloroquine. Seminal vesicle and prostate concentrations of salicylate and chloroquine were estimated via a novel analytic method involving a multilevel latent-variable model implemented by use of Bayesian methods. The geometric mean chloroquine semen/blood ratio was 4.02 (95% confidence interval [CI], 2.36-6.86); for salicylate, the primary metabolite of aspirin, the semen/blood ratio was 0.10 (95% CI, 0.08-0.14). The estimated mean prostate/seminal vesicle ratio for salicylate, 0.38 (95% CI by Bayesian methods, 0.12-0.73), was consistent with our hypothesis that salicylate would achieve higher concentrations in the seminal vesicle than in the prostate. Chloroquine, however, did not demonstrate a statistically significant seminal vesicle/prostate difference (4.41; 95% CI by Bayesian methods, 0.14-30.52). We successfully demonstrated the quantitative, noninvasive estimation of drug concentrations in the prostate gland fluid distinct from the seminal vesicle fluid using our optimized method of split-ejaculate collection and a novel mixed-effects model with Bayesian estimation. Our methods can be applied to gland-specific quantitation of drugs and other substances of interest, thus enabling pharmacokinetic, pharmacodynamic, and pathophysiologic studies to inform rational therapeutics within different glands of the male genital tract.
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