Protein-Free Efavirenz Concentrations in Cerebrospinal Fluid and Blood Plasma Are Equivalent: Applying the Law of Mass Action To Predict Protein-Free Drug Concentration

摘要: Efavirenz (EFV) is one of the most commonly prescribed antiretroviral drugs (ARVs) for treatment HIV. Highly protein-bound drugs, like EFV, have limited central nervous system (CNS) penetration when measured using total drug concentration gradients between blood plasma (BP) and cerebrospinal fluid (CSF). However, more relevant pharmacologically active protein-free concentrations are rarely assessed directly in clinical studies. Using paired BP CSF samples obtained from 13 subjects on an EFV-containing regimen, both EFV were determined. Despite a median (interquartile range [IQR]) BP/CSF ratio 134 (116 to 198), was 1.20 (0.97 2.12). (IQR) protein binding 99.78% (99.74 99.80%) 76.19% (74.47 77.15%) CSF. In addition, law mass action vitro-derived EFV-human serum albumin dissociation constant, we demonstrated that predicted BP, 4.59 ng/ml (4.02 9.44 ng/ml), compared well observed 4.77 (3.68 6.75 ng/ml). Similar results also seminal plasma. This method provides useful predictive tool estimating varied anatomic compartments. Our equivalent do not support prior concerns CNS as pharmacological sanctuary EFV. As ARVs may increase our understanding HIV-associated neurological dysfunction effect, assessment other highly warranted.