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.
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Keywords
Food-drug interaction , Bioavailability
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