The study investigates the critical role of transporters in drug absorption and elimination, emphasizing their influence on pharmacokinetics, therapeutic efficacy, and safety. Transporters such as organic anion-transporting polypeptides (OATPs) and P-glycoprotein (P-gp) mediate the influx and efflux of drugs across cellular membranes, significantly impacting bioavailability and systemic clearance. The objectives included identifying key transporters, analyzing their substrate specificity, and assessing the effects of genetic polymorphisms and environmental factors on their activity. A combination of in vitro assays, in vivo studies, and genetic analyses was employed. Cell lines like Caco-2 and HEK293, along with rodent models, were used to evaluate transporter functionality, while high-performance liquid chromatography and next-generation sequencing provided precise quantification and genetic insights.

The results demonstrated significant modulation of transporter activity by pharmacological agents and genetic variations. Rifampin inhibited OATP1B1 activity, reducing uptake rates by over 50%, while P-gp activation doubled the efflux ratio of specific substrates. Polymorphisms in the SLCO1B1 gene (c.521T>C) were associated with a 40% reduction in OATP1B1-mediated drug uptake, corroborated by increased plasma drug levels in preclinical models. Drug-drug interaction studies revealed a 3.2-fold increase in substrate AUC upon P-gp inhibition, highlighting the clinical implications of transporter modulation. High-fat diets reduced P-gp expression by 25%, demonstrating the impact of environmental factors.