Pharmacokinetic Interaction of Favipiravir with Amlodipine in Local Iraqi Rabbits (Oryctolagus cuniculus)

Abstract

Favipiravir is an effective anti-viral drug used to treat COVID-19, which is metabolized by aldehyde oxidase (AO) and xanthine oxidase (XO). This study investigated drug–drug interactions between Favipiravir and Amlodipine, an AO inhibitor, in healthy rabbits. A total of 20 local rabbits (Oryctolagus cuniculus), weighted between 2 and 2.5 kg, were divided into two equal groups: HFav. (dosed with distilled water for two weeks before administration of 40 mg/kg.BW of Favipiravir single oral dose) and HFav.+Am (dosed 0.5 mg/kg.BW of Amlodipine orally daily for two weeks before administration of 40 mg/kg.BW of Favipiravir single oral dose). Blood samples were taken from the marginal ear vein after 0.15, 0.30, 0.45, 1, 2, 4, 6, 8, 12, 24, 36, 48, and 72 hours. Thereafter, a high-performance liquid chromatograph (HPLC) technique assessed the drug plasma concentration. Amlodipine prolonged the time taken (Tmax) for Favipiravir to reach maximum concentration (Cmax) in the systemic circulation, decreased maximum serum concentration (Cmax), eliminated half-life, and increased the area under the curve (AUC). Furthermore, the results revealed that Amlodipine had reduced the clearance per unit time (Cl/f) when co-administered with Favipiravir. In conclusion, the concomitant administration of Amlodipine with Favipiravir caused substantial changes in the pharmacokinetic profile of Favipiravir. Therefore, the dosage rate adjustment of Favipiravir is recommended.