A pharmacokinetic approach to the establishment of biopharmaceutic characteristics of different acetylsalicylic acid formulations in man.
Eleven acetylsalicylic acid (ASA) formulations were administered to 26 healthy volunteers in a cross-over design. The properties of the preparations differed from conventional, effervescent, buffered to buccal. The objectives of this study were: Consideration of the general aspects of a biopharmaceutical study: which parameter for which biopharmaceutic characteristic? Measurement of the kinetic parameters of ASA: first-pass effect, mean residence time, mean appearance time, total body clearance, apparent volume of distribution, half-lives, etc. Comparison of the formulations. Most of the formulations yield mean residence times for ASA of 0.3-1.0 h, which do not differ significantly (p greater than 0.05). For most of the products the first-pass effect is about 40 per cent; the average values of the apparent volume of distribution and whole body clearance, corrected for the first-pass effect, are about 201 and 650 ml min-1, respectively. Peak levels are reached slowly for the buccal formulations, and rapidly for the buffered products. It is difficult, especially for ASA, to characterize the gastro-intestinal absorption with pharmacokinetic model parameters, because the first-pass effect is large and often elimination of ASA is faster than absorption. The model-independent approach has the special advantages of calculating reliable pharmacokinetic parameters, and creating theoretical possibilities to characterize the absorption patterns of the different formulations in a quantitative way. No significant differences in the values of the parameters are found between most of the formulations. The ASA first-pass effect is reasonably constant and buccal application has no advantage. Enteric coating of the outer layer of ASA formulations causes inconsistent absorption and may be categorized under 'artificial mistakes'.
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Raghoebar
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Vrancx
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Van Ginneken
D000293:Adolescent; D000328:Adult; D001241:Aspirin / Q000097:blood / Q000378:metabolism*; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D013607:Tablets
D013607:Tablets; D001241:Aspirin