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.
Highlights
For immediate-release drug products belonging to Biopharmaceutical Classification System Class II, III and IV as well as for all modified-release drug products, food intake significantly impacts the in vivo release and absorption of the active components
Present paper reports the effect of food on pharmacokinetics of omeprazole and the statistical analysis of the measured peak areas of the internal standard lansoprazole added to plasma before extraction of the active substance, throughout three bioequivalence studies performed in our laboratory: two in fasting conditions and another one in both fasting and fed conditions
Variable pharmacokinetics in both fasting and fed conditions is more obvious after examination of the clusters of plasma level curves presented in figure 2
Summary
In the case of generic drugs, pharmacokinetic studies are not required and are restricted following ethic considerations [20], a good alternative being to valuate data from bioequivalence studies undertaken as surrogate of clinical trials for testing therapeutic equivalence [21]. Even more simplified models of food effects are obtained by the study of the release kinetics of active substances from drug products in media containing non-physiological surface active agents. These simplified models are validated by correlation with in vivo pharmacokinetics data obtained in fasting and fed conditions [24]. Present paper reports the effect of food on pharmacokinetics of omeprazole and the statistical analysis of the measured peak areas of the internal standard lansoprazole added to plasma before extraction of the active substance, throughout three bioequivalence studies performed in our laboratory: two in fasting conditions and another one in both fasting and fed conditions. The linearity assessment was performed using a 7 point calibration curve in the range 0.025-2.5μg/mL The injection volume was 100 μL
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