The Male Genital Tract Is Not a Pharmacological Sanctuary From Efavirenz

Many antiretroviral (ARV) drugs have large blood plasma‐to‐seminal plasma (BP/SP) concentration ratios. Concern exists that these drugs do not adequately penetrate the male genital tract (MGT), resulting in the MGT becoming a “pharmacological sanctuary” from these agents, with ineffective MGT concentrations despite effective blood concentrations. Efavirenz (EFV) is the most highly protein‐bound ARV drug, with >99% binding in blood plasma and the largest BP/SP total EFV concentration ratio, reportedly ranging from 11 to 33. To evaluate protein binding as an explanation for the differences between the drug concentrations in blood and semen, we developed a novel ultrafiltration method, corrected for the duration of centrifugation, to measure protein binding in the two matrices. In six subjects, protein‐free EFV concentrations were the same in blood and semen; the median (interquartile range (IQR)) protein‐free EFV SP/BP ratio was 1.21 (0.99–1.35); EFV protein binding was 99.82% (99.79–99.86) in BP and 95.26% (93.24–96.67) in SP. This shows that the MGT is not a sanctuary from EFV. Clinical Pharmacology & Therapeutics (2011) 90 1, 151–156. doi: 10.1038/clpt.2011.99