Effect of food-drug interaction on oral drug bioavailability
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Date
2006
Authors
Sheau Chin, Lim
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Abstract
The present study was conducted to investigate potential interactions between some
common food constituents (capsaicin; caffeine; piperine) and substrate drugs of Pglycoprotein
(P-gp) and/or Cytochrome P450 subfamily CYP3A (CYP3A). Capsaicin is
found in Capsicum fruits (chillies), whereas caffeine is found in many common food and
beverages like coffee while piperine is a major alkaloid from pepper. Diltiazem and
rifampicin, which are known substrates of both P-gp and CYP3A, were used as model
drugs. Two high-performance liquid chromatographic (HPLC) methods with the required
specificity and sensitivity were successfully developed for determination of the two
respective compounds in rat/human plasma. Both methods also possessed good
precision and accuracy.
All studies were carried out according to a 2-way crossover study design using SpragueDawley
rats, where both drugs were administered with and without co-administration of
each food constituent. The influence of each food constituent was studied by giving it as
a single dose as well as 7 daily doses. In the single dose study, the model drugs were
given half an hour after the food constituent while in the multiple dose study, they were
given half an hour after the last dose of the food constituent. The respective doses of
diltiazem, rifampicin, capsaicin, caffeine and piperine used were 12, 10, 4, 6 and 20
mg/kg body weight of the rats.
In the study with capsaicin, no significant increase (p>0.05) in bioavailability was
observed with both diltiazem and rifampicin when the animals were treated with either a
single capsaicin dose or 7 daily consecutive doses, although their bioavailability were
found to be slightly increased by 1.1 and 1.2 times, respectively. However, in the case of
caffeine, the extent of absorption of diltiazem and rifampicin was found to be
significantly increased (p<0.05) by 1.4 and 1.5 times, respectively when co-administered
with a single caffeine dose. On multiple caffeine administration, the bioavailability of the
two model drugs was also found to be significantly (p<0.05) increased by 1.4 and 1.3
times, respectively. Interestingly, in a separate study where the rats were given 7 daily
doses of caffeine alone, its bioavailability determined after the last dose was found to be
significantly reduced (p<0.05) compared to that determined afte_r the first dose.
However, no significant difference (p>0.05) in bioavailability was observed when only
two doses were given 6 days apart. Nevertheless, both single and multiple dose
administration of caffeine were found to significantly alter the bioavailability of the two Pgp
and CYP3A substrate drugs.
As for piperine, even though it has been patented as a bioavailability enhancer, no
significant increase in bioavailability (p>0.05) was observed with both diltiazem and
rifampicin in the present study, whether piperine was given as a single dose or in
multiple doses. Thus, its utility as a bioavailability enhancer is controversial.
Description
Keywords
Food-drug interaction , Bioavailability