[Role of food interaction pharmacokinetic studies in drug development. Food interaction studies of theophylline and nifedipine retard and buspirone tablets].
Due to several mechanism, meals may modify the pharmacokinetics of drug products, thereby eliciting to clinically significant food interaction. Food interactions with the drug substance and with the drug formulation should be distinguished. Food interaction of different drug products containing the same active ingredient can be various depending on the pharmaceutical formulation technology. Particularly, in the case of modified release products, the food/formulation interaction can play an important role in the development of food interaction. Well known example, that bioavailability of theophylline can be influenced in different way (either increased, decreased or unchanged) by concomitant intake of food in the case of different sustained release products. The role and methods of food interaction studies in the different kinds of drug development (new chemical entity, modified release products, generics) are reviewed. Prediction of food effect response on the basis of the physicochemical and pharmacokinetic characteristics of the drug molecule or formulations is discussed. The results of three food interaction studies carried out the products of EGIS Pharmaceuticals Ltd. are also reviewed. The pharmacokinetic parameters of theophyllin 400 mg retard tablet were practically the same in both fasting condition and administration after consumption of a high fat containing standard breakfast. The ingestion of a high fat containing breakfast, increased the AUC of nifedipine from 259.0 +/- 101.2 ng h/ml to 326.7 +/- 122.5 ng h/ml and Cmax from 34.5 +/- 15.9 ng/ml to 74.3 +/- 23.9 ng/ml in case of nifedipine 20 mg retard tablet, in agreement with the data of literature. The statistical evaluation indicated significant differences between the pharmacokinetic parameters in the case of two administrations (before and after meal). The effect of a high fat containing breakfast for a generic version of buspiron 10 mg tablet and the bioequivalence after food consumption were studied in a single-dose, three-way (test and reference products administered after consumption of standard breakfast, as well as test product in fasting condition), cross-over, food effect bioequivalence study. According to the results, the test product--which, in a former study proved to be bioequivalent with the reference product in fasting state--is bioequivalent with the reference product under feeding conditions and the food intake influenced the pharmacokinetics of the test tablets.
Drabant
S
S
EGIS Gyógyszergyár Rt., Kutatási Igazgatóság, Farmakokinetikai Kutató Laboratórium, Budapest.
Klebovich
I
I
Gachályi
B
B
Renczes
G
G
Farsang
C
C
D002065:Buspirone / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004041:Dietary Fats; D018565:Food-Drug Interactions; D006801:Humans; D008657:Metabolic Clearance Rate; D009543:Nifedipine / Q000493:pharmacokinetics*; D019518:Postprandial Period; D013806:Theophylline / Q000493:pharmacokinetics*
D004041:Dietary Fats; D013806:Theophylline; D009543:Nifedipine; D002065:Buspirone