A Novel Translational Pharmacokinetic Investigation of Candidate Phytochemicals from Nigerian Medicinal Plants for Antiretroviral Augmentation

Several Nigerian medicinal plants contain phytochemicals with documented in vitro antiretroviral activity, yet translational pharmacokinetic investigations assessing their systemic bioavailability, metabolic stability, and potential for antiretroviral augmentation are entirely absent from the literature. This study conducted a novel translational pharmacokinetic investigation of three candidate phytochemicals identified from a prior in vitro antiretroviral screening programme of Nigerian medicinal plants. Selected compounds were oleanolic acid from Ximenia americana, azadirachtin derivatives from Azadirachta indica, and luteolin from Moringa oleifera. In vitro ADME profiling encompassed aqueous solubility, LogP, plasma protein binding, microsomal metabolic stability, CYP450 inhibition/induction potential, and Caco-2 permeability. Lead compounds demonstrating acceptable ADME profiles underwent formulation into lipid-based drug delivery systems to address permeability and solubility limitations. In vivo single-dose pharmacokinetic studies in Wistar rats established plasma concentration-time profiles, bioavailability, tissue distribution, and elimination parameters. Drug interaction studies assessed pharmacokinetic interactions with efavirenz at the CYP3A4 and P-glycoprotein level. Oleanolic acid in self-emulsifying drug delivery formulation demonstrated systemic bioavailability of 31.4 percent and minimal CYP3A4 interaction potential. Luteolin showed significant P-glycoprotein inhibition that enhanced efavirenz CNS penetration by 2.1-fold in murine models. The study provides novel translational pharmacokinetic data supporting the scientific basis for further clinical development of Nigerian phytochemical antiretroviral augmentation candidates.

Keywords: phytochemicals, antiretroviral augmentation, translational pharmacokinetics, Nigerian medicinal plants, HIV