The Effect of Piperine on Pharmacokinetics of Phenytoin in Healthy Volunteers

Abstract

Pharmacokinetics of phenytoin were studied in healthy subjects. In a crossover study five volunteers received either a single oral dose (300 mg) of phenytoin alone or in combination with multiple doses of piperine (20mg x 7 days) followed by an oral dose of phenytoin. Blood samples were col-lectedat0.5, 1,2,3,4,8, 12,24,and48hafter drug administration and analysed for phenytom by the enzyme multiplied immunoassay technique (EMIT). The results obtained revealed that a single daily dose of piperine for 7 days decreased the absorption haiflife (P < 0.05), prolonged the elimination halflife (P < 0.01), and produced a higher area under the drug concentration curve (P < 0.05) in comparison to phenytoin alone. It is therefore concluded that piperine on multiple dose administration alters the pharmacokinetic parameters of the antiepileptic.

Bioavailability enhancers of herbal origin: An overview

“…Even at higher concentration of 50 mg/mL, piperine alone shows no inhibitory effect for the growth of M. smegmatis but increases the inhibitory potential of rifampicin when given with it in ratio of 24:1 at the lower concentration of 0.125-0.5 mg/mL. The binding ability of rifampicin to RNA polymerase is enhanced by piperine [112] .…”

Structure–activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities

“…2±7 We postulated that the use of piperine in the form of piper species in several traditional herbal formulations might have been responsible for the enhancement of drug bioavailability consequent to modulation of drug metabolism. 2 Subsequently, it was shown to enhance the bioavailabilty of phenytoin in healthy volunteers, 8 reduce a¯atoxin B1 binding of DNA 9 and protected hepatoma cells 4 and V79 constructs of rat CYP2B1 10 in cultures from cytotoxicity and genotoxicity of AFB 1 by impairing CYP mediated activation of the mycotoxin. Piperine also produced dierential inhibition of glucuronidation in guinea pig enterocytes and rat liver, while conjugated double bonds appeared essential for in vitro inhibition of hepatic UDP-glucose dehydrogenase 6 irrespective of the oxidation state of piperidine or methylenedioxyphenyl (MDP) rings.…”

Molecular targets of pepper as bioavailability enhancer

“…Pepper caused two fold increases in bioavailability of propranolol by inhibiting its metabolism by the liver and thereby excellent antihypertensive effect was obtained with low dose of propranolol (Bano et al, 1991). Similar results were also obtained when piperine was administered along with theophylline, an antiasthmatic drug and phenytoin, an anti-epileptic drug and these were due to inhibition of biotransforming enzymes in liver as well as slowing down the elimination rate (Bano et al, 1978;Bano et al, 1991). Piperine coadministered with a formulation containing rifampicin, pyrazinamide and isoniazid has been tested in human volunteers where, the comparative levels and peak concentration of these drugs were higher in the presence of piperine.…”