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PHARMACOKINETICS |
From the Division of Clinical Pharmacology, Department of Medicine, School of Medicine (Dr Cao, Ms Radebaugh, Mr Fuchs, Dr Hendrix); Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland (Dr Caffo); and the Department of Biostatistics, School of Medicine, Vanderbilt University, Nashville, Nashville, Tennessee (Dr Choi).
The accessory glands of the male genital tract are the sites of several major health problems, including benign prostatic hyperplasia, prostate cancer, and human immunodeficiency virus (HIV) transmission. We aimed to validate and improve our noninvasive method for the quantitation of drug concentrations in these physiological subcompartments. Twenty-seven men were dosed with 100 mg desipramine (a weak base) and 975 mg aspirin (a weak acid) and ejaculated their semen in 1 pass across 5 compartments of a collection device 2.5 hours later. A Bayesian latent-variable model previously developed by our group was further advanced for the estimation of drug concentrations in prostate and seminal vesicles based on drug and biomarker concentrations in the split ejaculate. Under normality assumptions, desipramine concentration (with 95% credible intervals) in prostate and seminal vesicles were 27 (8.3-52) ng/mL and 7.6 (4.0-11) ng/mL, respectively; salicylate concentration in prostate and seminal vesicles were 2.0 (0.093-6.5) µg/mL, and 9.9 (8.2-12) µg/mL, respectively. The prostate-to-seminal vesicles concentration ratio was 0.20 (0.0087-0.75) for salicylate and 3.6 (0.91-9.9) for desipramine. We conclude that our quantitative analysis along with the split ejaculate method is sensitive, reproducible, and applicable for the assessment of pharmacokinetics of the accessory glands of the male genital tract.
Key Words: Male genital tract semen quantitative clinical pharmacology modeling pharmacokinetics
Address for correspondence: Dr. Craig W. Hendrix, Harvey 502, 600 N. Wolfe Street, Baltimore, MD, 21287; e-mail: chendrix{at}jhmi.edu.
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