Quantitative assessment of seminal vesicle and prostate drug concentrations by use of a noninvasive method.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Ndovi
Themba T
TT
Department of Medicine, Division of Clinical Pharmacology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Choi
Leena
L
Caffo
Brian
B
Parsons
Teresa
T
Baker
Sharon
S
Zhao
Ming
M
Rohde
Charles
C
Hendrix
Craig W
CW
D000328:Adult; D000465:Algorithms; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis / Q000493:pharmacokinetics; D000962:Antimalarials / Q000032:analysis / Q000493:pharmacokinetics; D001241:Aspirin / Q000032:analysis / Q000493:pharmacokinetics; D001499:Bayes Theorem; D015415:Biomarkers; D002738:Chloroquine / Q000032:analysis / Q000493:pharmacokinetics; D005632:Fructose / Q000032:analysis; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D008297:Male; D011467:Prostate / Q000737:chemistry / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000032:analysis; D011786:Quality Control; D012044:Regression Analysis; D012661:Semen / Q000737:chemistry; D012669:Seminal Vesicles / Q000737:chemistry / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000962:Antimalarials; D015415:Biomarkers; D005632:Fructose; D002738:Chloroquine; D017430:Prostate-Specific Antigen; D001241:Aspirin