2026-04-20T14:25:22Z https://www.peertechzpublications.org/oai-pmh

oai:www.peertechzpublications.org:10.17352/ijpsdr.000059 2026-04-14 PTZ.IJPSDR:VOL12

Repaglinide-Indinavir Pharmacokinetic and Pharmacodynamic Interaction: Non-Clinical Evaluation in Hepatic and Diabetic Impairment models Jeevan Karthik M Aakarsha T Lokesh J Manaswini C Rameshbabu JSrinivas M<p>Background: Repaglinide, used for postprandial glucose control, is extensively metabolized by cytochrome P450 enzymes and transported by OATP and P-glycoprotein, making it susceptible to pharmacokinetic interactions. Indinavir, an antiviral protease inhibitor, affects metabolic and transport pathways, thereby altering the pharmacokinetic and pharmacodynamic profile of repaglinide. This study investigated the interaction between repaglinide and indinavir in healthy rats and in rat models of diabetes and hepatic impairment.</p><p>Methods: Clinical doses of indinavir and repaglinide were converted to rat-equivalent doses using the Body Surface Area (BSA) method. Healthy, diabetic, and hepatic-impaired rats were administered indinavir (78 mg/kg, P.O), followed by repaglinide (0.5 mg/kg, P.O). Plasma concentrations of repaglinide were determined, and pharmacokinetic parameters, including maximum plasma concentration (Cmax), Area Under the Concentration–time curve (AUC), elimination half-life (t½), and plasma clearance (CL), were evaluated. Blood glucose levels were also measured to assess pharmacodynamic effects.</p><p>Results: In the presence of indinavir, repaglinide exhibited significantly altered pharmacokinetics in normal (P &lt; 0.005), diabetic (P &lt; 0.0001), and hepatic-impaired (P &lt; 0.0001) rats, characterized by increased maximum plasma concentration (Cmax), Area Under the Concentration–time curve (AUC), and elimination half-life (t½), along with a significant reduction in plasma clearance (CL) across all groups compared with repaglinide alone. Pharmacodynamically, repaglinide in combination with indinavir produced a markedly greater (P &lt; 0.0001) hypoglycemic effect in diabetic and hepatic-impaired rats than repaglinide administered alone.</p><p>Conclusion: The study demonstrates a significant pharmacokinetic and pharmacodynamic interaction between indinavir and repaglinide, characterized by enhanced bioavailability and reduced total body clearance of repaglinide. These effects are likely mediated by the inhibitory action of indinavir on cytochrome P450 enzymes, as well as on OATP and P-glycoprotein transporters.</p> International Journal of Pharmaceutical Sciences and Developmental Research - Peertechz Publications 2026-04-14 Research Article https://doi.org/10.17352/ijpsdr.000059 en Copyright © Jeevan Karthik M et al.