INFLUENCE OF PIPERINE ON PHARMACOKINETICS OF ZOLMITRIPTAN IN RATS: INVOLVEMENT OF CYP3A METABOLISM
Ravi Prakash Degala*, Govinda Rao Kamala, N. Suvarna Jyothi, P. Anusha and D. Surya Tejaswini
ABSTRACT
Zolmitriptan is a second generation triptan effective medicine used in the treatment of migraine headaches. Piperine (1-piperoylpiperidine) is the world’s first reported bio enhancer alkaloid was found to enhance bioavailability of structurally and therapeutically diverse drugs. It was main pungency principle in both black and long pepper. In this study the pharmacokinetic profile of zolmitriptan after oral administration of zolmitriptan (0.5mg/kg) alone and in combination with piperine (10mg/kg) to rats were investigated via validated HPLC method. The blood samples were collected at various time points such as 0(predose), 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 8.0, 12, 24 hours post treatment. As the Invivo pharmacokinetic studies had indicated, the Cmax, Tmax, AUC0-24, AUC0-∞, AUC%, AUMC0-24, AUMC0-∞, t1/2, MRT0-24and MRT0-∞ were increased by approximately 77.63%, 24%, 66%, 77.86%, 44.51%, 77.40%, 114.64%, 21.90%, 6.82% and 21.98% respectively, where as clearance and volume of distribution decreased by 50% and 32% when zolmitriptan co-administered with piperine. In conclusion, our study demonstrated that piperine significantly improved the Invivo bioavailability of zolmitriptan and the influence of piperine on the pharmacokinetics of zolmitriptan may be attributed to the inhibition of CYP3A and P-gp in rats. Further research needed to investigate detailed mechanism of improved bioavailability of zolmitriptan via its combination with piperine. This observation suggests the possibility that the combination of piperine with other CYP3A and P-gp dual substrates may also improve bioavailability.
Keywords: Zolmitriptan, Piperine, Bioavailability, Pharmacokinetics, P-glycoprotein, Cytochrome P-450.
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