low-dose aspirin pharmacokinetics
Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Summary The pharmacokinetics of low-dose aspirin and the resulting salicylic acid were studied in 6 healthy volunteers. Each received a single 50-mg dose of (1) oral modified release capsules, (2) oral solution and (3) intravenous solution. The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose. The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng·ml−1) was 221 and 191 after modified release for single and chronic dosing respectively, 1323 after the oral solution and 6000 after intravenous injection; the time to achieve this maximum concentration (tmax, h) was 3.42 and 3.02 after modified release for single and chronic dosing respectively, and 0.29 after the oral solution; the area under the plasma drug concentration versus time curve (AUC, µg·h·ml−1) was 0.38 and 0.27 after modified release single and chronic dosing respectively, 0.68 after the oral solution and 1.57 after intravenous injection. The elimination of aspirin after the two solutions was at least biphasic. The terminal phase rate constant ranged from 1.52 h−1 after intravenous injection to 1.88 h−1 after the oral modified release form. The absorption of the oral forms of aspirin was complete as reflected by the total recovery of the doses as salicylic acid in urine. The pharmacokinetic parameters for salicylic acid showed similar tmax and Cmax for the oral solution and intravenous injection but, as for aspirin, Cmax was least and tmax greatest when the modified release form was used. After 7 days of modified release aspirin platelet aggregation and thromboxane formation in response to collagen and arachidonate were markedly inhibited. There was no inhibition of ADP-induced aggregation, but thromboxane production in response to ADP was abolished.
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