Effect of piperine on the steady‐state pharmacokinetics of phenytoin in patients with epilepsy

Abstract

Piperine, the active principle of Piper longum, Piper nigrum and Zingiber officinalis, has been reported to enhance the oral bioavailability of phenytoin in human volunteers. The objective of this study was to explore the effect of a single dose of piperine in patients with uncontrolled epilepsy on the steady-state pharmacokinetics of phenytoin. Two groups of 10 patients each receiving either a 150 mg or 200 mg twice daily dose of phenytoin were selected. Twelve hours after the night dose, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h after administration of phenytoin. On the next study day, piperine 20 mg was administered along with phenytoin and samples were collected similarly. The mean plasma drug concentrations at different time points and the pharmacokinetic parameters before and after piperine administration were compared by Student's t-test. Piperine increased significantly the mean plasma concentration of phenytoin at most of the time points in both dose groups. There was a significant increase in AUC((0-12h)) (p < 0.01), C(max) (p < 0.001) and K(a) (p < 0.05) whereas the changes in K(el) and t(max) were not significant. The results showed that piperine enhanced the bioavailability of phenytoin significantly, possibly by increasing the absorption.

Search for New Type of PPARγ Agonist-Like Anti-diabetic Compounds from Medicinal Plants

“…[40][41][42][43][44] In our study, the "area-under-the-curve" (AUC) of 11 increased following in vivo administration of the extract, suggesting that the other constituents in the extract inhibit the metabolism of 11. 19) Previous studies have demonstrated that flavonoids and/or flavonoid-rich fractions ameliorate experimental diabetes in mice and rats.…”

Enhanced oral bioavailability of piperine by self-emulsifying drug delivery systems:in vitro, in vivoandin situintestinal permeability studies

“…The piperine is one of the most well-known components because of its high medicinal properties (Bhardwaj et al, 2002;Gao & Morozowich, 2006). In Indian medicine, the piperine and its derivatives were always used for treating epilepsy, headache and so on (Pattanaik et al, 2006). As increasingly popular modern-day uses of piperine, it has been reported to inhibit oxidative stress, antifungal, anti-inflammatory activity and anti-tumor (Sunila & Kuttan, 2004;Bezerra et al, 2008;Ee et al, 2010).…”

Simultaneous determination of etoposide and a piperine analogue (PA-1) by UPLC–qTOF-MS: Evidence that PA-1 enhances the oral bioavailability of etoposide in mice

“…has been shown to be effective as a bioavailability enhancer of several drugs and other pharmacologically active substances (phenytoin, propranolol, theophylline, nevirapine, beta-lactam antibiotics, curcumin, coenzyme Q10, and epigallocatechin) in animals and human volunteers [1][2][3][4][5][6][7]. Recently a novel series of substituted piperine analogues have been synthesized in our laboratory [8], for the purpose of identifying potential leads as bioenhancer(s) for anti-cancer agents, majority of which exhibit low/variable oral bioavailability.…”