Many antiretroviral drugs have large blood plasma (BP): seminal plasma (SP) ratios based on total drug concentrations. Concern exists that these drugs don’t adequately penetrate the male genital tract (MGT), resulting in a pharmacologic sanctuary with ineffective MGT concentrations despite effective blood concentrations. Efavirenz (EFV) is the most highly protein-bound antiretroviral 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 the explanation for blood-semen differences, we developed a novel centrifugation time corrected ultrafiltration method to measure protein binding in both matrices. In 6 subjects, protein-free EFV concentrations were the same in blood and semen; median (IQR) protein-free EFV SP: BP ratio calculated for each individual 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. The MGT is not a pharmacological sanctuary from efavirenz.
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