22.6 Bioavailability of Drugs
Piperine, an essential constituent of black and long peppers, has been mentioned to
boost the bioavailability of drugs. The goal of the present studies was to understand
piperine ’s interaction with intracellular drug biotransforming processes in vitro and
in vivo liver tissue. During in vitro findings in rat filtrate, piperine suppressed
removal of the hydroxy group from aryl hydrocarbon, N-methyl group from
ethylmorphine, O-ethyl group from 7-ethoxycoumarin, and 3-hydroxy-benzo(a)
pyrene glucuronidation in graded order. Piperine suppression of certain consequences from 3-methylcholanthrene- and phenobarbital-treated rats in post mitochondrial filtrate was identical to those controls. Piperine suppression of
arylhydrocarbon hydroxylase from rats treated with 3-methylcholanthrene was
similar to 7,8-benzoflavone. Piperine has induced noncompetitive suppression of
hepatic hydroxylase from non-treated and 3-methylcholanthrene-treated animals
with a Ki of thirty microM below the significant Km of arylhydrocarbon hydroxylase detected at controls. Additionally, the kinetic studies of ethylmorphineN-demethylase suppression from monitoring rat hepatic microsomes showed noncompetitive suppression with significant 0.8 mM Km and thirty-five microM Ki.
Such studies have shown that piperine is a non-specific drug metabolic inhibitor
that displays no distinction between the various cytochrome P-450. Oral piperine
administration in rats significantly suppressed the functions of the hepatic arylhydrocarbon hydroxylation and UDP-glucuronyltransferase. Absolute arylhydrocarbon hydroxylation inhibition detected within 1 h was restored to normal range
within 6 h. Piperine pretreatment extended in time of sleeping and paralysis in
animals at 50% of the SKF-525A dose. These verdicts confirm that piperine as
effective drug metabolism inhibitor (Atal et al. 1985).
22.7 Effect on Enzymes
In vitro and in vivo modulation of drug-metabolizing enzymes by piperine was
investigated in microsomes of rats and guinea pigs. In vitro piperine caused
concentration-related inhibition (50% at 100 microM) of arylhydrocarbon
hydroxylase (AHH) and 7-ethoxycourmarin deethylase (7ECDE) activities, which
were comparable in control and 3-methylcholanthrene (3MC) treated rats. In guinea
pig microsomes, however, piperine caused strong inhibition at lower concentrations
(35% at 10 microM) and relatively much lesser inhibition with further increase in
piperine concentrations. A Dixon plot of the kinetic data of both AHH and 7ECDE
indicated noncompetitive inhibition with a Ki of approx. 100 microM. In vivo,
piperine given at a dose of 25 mg/kg body wt to rats caused a maximal inhibition at
1 h of both the enzymes, while only AHH returned to normal value within 4 h.
Similarly, upon daily treatment of piperine (15 mg/kg body wt) to rats for 7 days,
7ECDE was consistently inhibited, while AHH showed faster recovery. Piperine
22 Piperine: Sources, Properties, Applications …
763
Piperine, an essential constituent of black and long peppers, has been mentioned to
boost the bioavailability of drugs. The goal of the present studies was to understand
piperine ’s interaction with intracellular drug biotransforming processes in vitro and
in vivo liver tissue. During in vitro findings in rat filtrate, piperine suppressed
removal of the hydroxy group from aryl hydrocarbon, N-methyl group from
ethylmorphine, O-ethyl group from 7-ethoxycoumarin, and 3-hydroxy-benzo(a)
pyrene glucuronidation in graded order. Piperine suppression of certain consequences from 3-methylcholanthrene- and phenobarbital-treated rats in post mitochondrial filtrate was identical to those controls. Piperine suppression of
arylhydrocarbon hydroxylase from rats treated with 3-methylcholanthrene was
similar to 7,8-benzoflavone. Piperine has induced noncompetitive suppression of
hepatic hydroxylase from non-treated and 3-methylcholanthrene-treated animals
with a Ki of thirty microM below the significant Km of arylhydrocarbon hydroxylase detected at controls. Additionally, the kinetic studies of ethylmorphineN-demethylase suppression from monitoring rat hepatic microsomes showed noncompetitive suppression with significant 0.8 mM Km and thirty-five microM Ki.
Such studies have shown that piperine is a non-specific drug metabolic inhibitor
that displays no distinction between the various cytochrome P-450. Oral piperine
administration in rats significantly suppressed the functions of the hepatic arylhydrocarbon hydroxylation and UDP-glucuronyltransferase. Absolute arylhydrocarbon hydroxylation inhibition detected within 1 h was restored to normal range
within 6 h. Piperine pretreatment extended in time of sleeping and paralysis in
animals at 50% of the SKF-525A dose. These verdicts confirm that piperine as
effective drug metabolism inhibitor (Atal et al. 1985).
22.7 Effect on Enzymes
In vitro and in vivo modulation of drug-metabolizing enzymes by piperine was
investigated in microsomes of rats and guinea pigs. In vitro piperine caused
concentration-related inhibition (50% at 100 microM) of arylhydrocarbon
hydroxylase (AHH) and 7-ethoxycourmarin deethylase (7ECDE) activities, which
were comparable in control and 3-methylcholanthrene (3MC) treated rats. In guinea
pig microsomes, however, piperine caused strong inhibition at lower concentrations
(35% at 10 microM) and relatively much lesser inhibition with further increase in
piperine concentrations. A Dixon plot of the kinetic data of both AHH and 7ECDE
indicated noncompetitive inhibition with a Ki of approx. 100 microM. In vivo,
piperine given at a dose of 25 mg/kg body wt to rats caused a maximal inhibition at
1 h of both the enzymes, while only AHH returned to normal value within 4 h.
Similarly, upon daily treatment of piperine (15 mg/kg body wt) to rats for 7 days,
7ECDE was consistently inhibited, while AHH showed faster recovery. Piperine
22 Piperine: Sources, Properties, Applications …
763