Impact of N-acyl piperidine (Piperine) from Piper nigrum on the pharmacokinetics of CYP3A substrate almotriptan in rats

Abstract

Almotriptan belongs to second-generation triptans, which were discovered and developed by Almirall for the treatment of severe migraine headaches. Piperine (N-acyl piperidine) is a plant alkaloid and a natural bioenhancer, which was found to reinforce the bioavailability of structurally and therapeutically different drugs. The study developed a validated high-performance liquid chromatography (HPLC) method for assessment of the pharmacokinetic profile after oral administration of almotriptan (1.2 mg/kg) alone and in combination with Piperine (10 mg/kg) in rats. Pharmacokinetic profile was determined at 0 (predose), 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 9, 12, and 24 hours post-treatment using blood samples. The results indicated that the percentage change of Peak Concentration (Cmax), Maximum Time for maximum concentration (Tmax), Area Under Curve (AUC0-24, AUC0-∞, AUC%), Area Under Moment Curve (AUMC0-24, AUMC0-∞), Half-life (T1/2), Mean Residence Time (MRT0-24, MRT0-∞), and volume of distribution (VD) were increased approximately 67.63%, 26.04%, 72.12%, 88.71%, 100.37%, 93.40%, 163.72%, 52.79%, 12.89%, 39.53%, and 25.80%, respectively. In contrast, clearance decreased by 50% when almotriptan was co-administered with Piperine. Piperine significantly improved the fraction of almotriptan that reached the rat's systemic circulation. Therefore, co-administration of piperine improved the bioavailability of almotriptan and could be attributed to the inhibition of CYP3A and P-gp in rats.