Estimation of the Effects of Food on the Pharmacokinetic Results in Bioequivalence Studies

Abstract

Paper presents the effect of food on the pharmacokinetics of omeprazole and on the extraction yield of its internal standard, lansoprazole. The experimental data were obtained over three bioequivalence studies performed by the authors. Statistical analysis of plasma level curves of omeprazole indicated that food induces a delay of the time of maximum concentrations, but had a lower effect on maximum concentration and area under curves. Peak areas of lansoprazole were not constant, presenting a similar pattern in all seven periods of the clinical experiment, both in feeding and fasting conditions: an increase after the standard meal at four hours from the administration of drug followed by relatively constant, but higher areas afterwards. Statistical analysis of data (1500 points) in the 3 - 6 h interval, i.e. from immediately before until two hours after food intake revealed a two phase effect: an initial decrease of areas followed by an increase to a higher level than in the preprandial conditions, leading to the appearance of a minimum in curves one hour after food intake. In almost all cases a good parabolic fitting of data was obtained, which is in agreement with authors previous results on extraction of ketoconazole from pasma in methylene chloride in the presence of bile salts. The increase of peak areas of lansoprazole from two hours after meal by 24 h lead to an artificial decrease of calculated omeprazole concentrations. This effect could explain the unexpected lack of food effect on the area under curve of omeprazole, observed in the comparison between areas in fasting and fed conditions.