[Pharmacokinetics after oral and intravenous administration of d,l-monolysine acetylsalicylate and an oral dose of acetylsalicylic acid in healthy volunteers].
We studied the ASA pharmacokinetics of single doses of 500 mg and 1000 mg of D,L-lysine-monoacetylsalicylate (Lys-ASA) administered both orally (Delgesic) and 500 mg parenterally (Aspisol) as well as 500 mg acetylsalicylate (ASA, Aspirin) in 13 healthy volunteers. Blood samples were taken before and at defined times up to 48 h after application of Lys-ASA and ASA. Analysis for ASA and its metabolite salicylic acid were performed by HPLC. All concentration versus time data were presented descriptively. As far as ASA was concerned, differences were assessed by means of ANOVA according to Friedman including post hoc Wilcoxon tests for each time point. Pharmacokinetic parameters were calculated based on a one-compartment model. The concentration vs. time curves after oral intake of 500 mg of ASA and Lys-ASA differed significantly (p < 0.001). Peak serum ASA concentrations (Cmax) were 6.8 mg/l for oral Lys-ASA and 2.7 mg/l for ASA per os. The corresponding tmax-values were 14.2 and 38.0 min. Absolute bioavailabilities for 500 mg doses were 75.4 and 63.4 pour cent, respectively. After intake of 100 mg and 1000 mg oral doses of Lys-ASA Cmax was 2.7 mg/l and 15.9 mg/l, tmax being 14.2 min for the 1000 mg dose. The shortest half-life was found after i.v. injection with 7.5 min. Metabolism was fast with maximum rise of salicylic acid concentration after injection of Lys-ASS. We conclude that concerning time dimension oral administration of Lys-ASA is almost equivalent to i.v. Lys-ASA and may be an alternative for i.v. administration in cases of acute heart attacks.
Raschka
C
C
Medizinische Klinik, Städtisches Klinikum Fulda, Pacelliallee 4, D-36043 Fulda.
Koch
H J
HJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged
D000894:Anti-Inflammatory Agents, Non-Steroidal; D008239:Lysine; D001241:Aspirin; C010395:acetylsalicylic acid lysinate