Effect of Naringin Co-administration on Oral Bioavailability of Efavirenz in Rabbit

Abstract

Efavirenz is a first line anti-retroviral drug belonging to category of non-nucleoside reverse transcriptase inhibitor (NNRTIs), However, it has variable bioavailability due to its limited aqueous solubility. Naringin is a bioavailability enhancer which has been used to increase bioavailability of several drugs. Therefore, the purpose of this study was to investigate the possibility of improving the bioavailability of Efavirenz using Naringin in experimental rabbits. The experimental rabbits were divided into four groups. Group I received Efavirenz 9.33 mg/kg, p.o (which corresponded to 200mg of human dose), Group II received Efavirenz 9.33mg/kg, + Naringin 20.8mg/kg, p.o; Group III received Efavirenz 28mg/kg, p.o (which corresponded to 600mg of human dose); Group IV received Efavirenz 28mg/kg + Naringin 20.8mg/kg, p.o. Afterwards, plasma from each group of rabbits was extracted and at fixed time interval drug plasma concentration was estimated using HPLC. Pharmacokinetic parameters of were determined for each group. Efavirenz (9.33mg/kg and 28mg/kg) - Naringin (20.8mg/kg) co-administration significantly increased absorption rate constant (Ka) and elimination rate constant (Kel), Cmax, T1/2, Tmax significantly. Efavirenz 9.33mg/kg - Naringin (20.8mg/kg) co-administration increased area under the curve significantly. The relative bioavailability of Efavirenz 9.33 mg/kg - Naringin (20.8mg/kg) co-administration and Efavirenz 28mg/kg - Naringin (20.8mg/kg) co-administration was found to be 113.77% and 106.75% respectively. Based on the results it can be concluded that Naringin co-administration increased the oral exposure of Efavirenz to some extent. Bioavailability of Efavirenz with Naringin was found to be higher than Efavirenz control.