title: The male genital tract is not a pharmacological sanctuary from efavirenz.
abstract: 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.
authors.affiliation: Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: L B
authors.initials: LB
authors.lastname: Avery
authors.forename: R P
authors.initials: RP
authors.lastname: Bakshi
authors.forename: Y J
authors.initials: YJ
authors.lastname: Cao
authors.forename: C W
authors.initials: CW
authors.lastname: Hendrix
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000378:metabolism; D000465:Algorithms; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood / Q000378:metabolism*; D048588:Benzoxazines / Q000097:blood / Q000378:metabolism*; D002498:Centrifugation; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D003956:Dialysis; D005837:Genitalia, Male / Q000378:metabolism*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D008297:Male; D011485:Protein Binding; D018894:Reverse Transcriptase Inhibitors / Q000378:metabolism*; D012661:Semen / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D014462:Ultrafiltration; D055815:Young Adult
chemical_list: D000418:Albumins; D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz