Impact of N-acyl piperidine (Piperine) from Piper nigrum on the Pharmacokinetics of CYP3A Substrate Almotriptan in Rats

Rajkiran Kolakota*, Akhil Bothsa, Vinodkumar Mugada
Department of Pharmacology, Vignan Institute of Pharmaceutical Technology, Visakhapatnam, AP 530049, India
Corresponding Author:; Tel: 0891-251122
Recieved Date: July 30, 2020; Accepted Date: August 22, 2020; Published Date: 28 August 2020
Citation: Kolakota R, Bothsa A, Mugada V. Impact of N-acyl piperidine (Piperine) from Piper nigrum on the Pharmacokinetics of CYP3A Substrate Almotriptan in Rats. Trop J Nat Prod Res. 2020; 4(8):378-384.
Copyright: © 2020 Kolakota et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 rats 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. 

Keywords: Almotriptan, Piperine, Bioavailability, Pharmacokinetics, P-glycoprotein, Cytochrome P-450.
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