High-pressure liquid chromatographic evaluation of cyclic paracetamol-acetylsalicylate and its active metabolites with results of a comparative pharmacokinetic investigation in the rat.
Like benorilate, its correlated open ester, MR 897, a cyclic ester between acetylsalicylic acid and paracetamol, gives rise to acetylsalicylic acid, salicylic acid and paracetamol by enzymatic hydrolysis. An analytical method was developed, which detects parent drugs and active metabolites, in order to compare the pharmacokinetic and metabolic behaviour of the two products. The method was specifically validated for quantitative analysis of salicylic acid and paracetamol, which are the main systemic metabolites of both MR 897 and benorilate. Extraction from plasma or tissue homogenate was carried out in two steps with diethyl ether and acetate. Recovery of the analytical substances ranged from 82.7% for paracetamol to 98.5% for salicylic acid. The results of a comparative pharmacokinetic investigation of MR 897 and benorilate in the rat confirm higher bioavailability and a more favourable plasma level profile with MR 897.
Marzo
A
A
B.T.B. Industria Chimica S.p.A., Laboratory of Drug Metabolism and Pharmacokinetics, Tribiano, Italy.
Quadro
G
G
Treffner
E
E
Ripamonti
M
M
Meroni
G
G
Lucarelli
C
C
D000082:Acetaminophen / Q000032:analysis* / Q000493:pharmacokinetics; D000083:Acetanilides; D000818:Animals; D001241:Aspirin / Q000032:analysis* / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012015:Reference Standards; D012459:Salicylates / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution
D000083:Acetanilides; D012459:Salicylates; D000082:Acetaminophen; C065883:MR 897; D001241:Aspirin