Study of Pharmacodynamic and Pharmacokinetic Interactions of Non‐nucleoside Reverse Transcriptase Inhibitors with Gliclazide in Animal Models

The objective of this study was to investigate the safety and effectiveness of the non‐nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine) with gliclazide by conducting pharmacodynamic interaction studies in rats (normal and diabetic) and rabbits, and pharmacokinetic (PK) interactions studies in rabbits. These studies were conducted with an oral dose of gliclazide, interacting drug (efavirenz/nevirapine) and their combination with adequate washout periods in between treatments (single dose and multiple dose study). The blood glucose, plasma insulin were analyzed by GOD/POD and radio immuno assay method respectively. The insulin resistance index and β‐cell function were determined by HOMA. The serum gliclazide levels were estimated by HPLC method and PK analysis was conducted by non‐compartmental analysis using WinNonlin software. In combination, efavirenz has significant (p<0.05) PK interaction with gliclazide by increasing gliclazide metabolism through CYP3A4 induction while nevirapine has no significant effect and found to be safe in combination with gliclazide. Since the interaction of efavirenz with gliclazide was seen in rodent & non‐rodent, they are likely to occur in humans also leading to decreased activity of gliclazide, which may need dosage adjustment and care should be taken when this combination is prescribed for the clinical benefit in diabetic patients.