Oral Bioavailability Enhancement of Efavirenz using Piperine coadministration in Experimental Rabbits

Background: Efavirenz, a first line anti-retroviral drug has variable bioavailability owing to its limited aqueous solubility. Piperine, a bioavailability enhancer has been often used to enhance the bioavailability of many drugs.

Objective: The present study was aimed to investigate the possibility of improving the bioavailability of efavirenz using piperine.

Methods: Two doses of efavirenz 9.33 mg/kg and 28 mg/kg which corresponded to 200 and 600 mg/kg of human dose were selected. Single oral dose of efavirenz and piperine co administration was given to rabbit and at fixed time interval drug blood concentration was estimated by HPLC. Pharmacokinetic parameters of efavirenz and piperine co administration were determined.

Results: Efavirenz 9.33 mg/kg co administration with piperine 20.8 mg/kg increased area under the curve significantly at p<0.01 and Cmax at p<0.05 compared to efavirenz control (9.33 mg/kg). The relative bioavailability of efavirenz and piperine co-administration was found to be 149.08%, i.e., higher than efavirenz control.  T1/2 of piperine co-administration was also increased significantly at p<0.05 compared to efavirenz control. Tmax of piperine co-administration was found to be 0.5 h, followed by efavirenz control i.e., 1 h. Co-administration of efavirenz (28 mg/kg) with piperine (20.8 mg.kg) significantly increased AUC and Cmax at p<0.001 compared to efavirenz control (28 mg/kg). The relative bioavailability of Piperine co-administration was found to be 158.92%, higher than efavirenz control. There was significant increase in T1/2 of piperine co-administration at p<0.01 compared to efavirenz control. Tmax of piperine co-administration and efavirenz were found to be same i.e., 1 h.

Conclusion: Based on the results it can be concluded that piperine co-administration significantly increases the oral exposure of efavirenz. Bioavailability of efavirenz with piperine was found to be higher than efavirenz control.