Comparative bioavailability of two oral metamizole formulations. Influence of the acetylation phenotype.
The bioavailability of the four metabolites of metamizole (CAS 68-89-3), 4-methyl-amino-antipyrine (4-MAA), 4-formyl-amino-antipyrine (4-FAA), 4-amino-antipyrine (4-AA) and 4-acetyl-amino-antipyrine (4-AcAA) was compared after oral administration of a test (Analgin) and a reference formulation, both containing 1 g of metamizole. The study was conducted in 12 healthy volunteers according to an open, randomized, cross-over design. The geometric mean of the area under the serum concentration-time curves (AUC) of 4-MAA for the test formulation was 87.61 (57.58-133.30) micrograms.h/ml and was similar to that for the reference formulation (86.83; 53.86-139.92 micrograms.h/ml). No statistically significant differences between test and reference formulation were found with respect to the rate of absorption (Cmax, tmax, 100 Cmax/AUC) of 4-MAA. For 4-FAA, 4-AA and 4-AcAA, the 90% confidence intervals of the bioavailability parameters lay also within the bioequivalence ranges. Four of the subjects were rapid and eight were slow acetylators. No differences were found between slow and rapid acetylators in the bioavailability of 4-MAA, the pharmacologically active metabolite of metamizole.
Bacracheva
N
N
Chair of Clinical Pharmacology, Medical Faculty, Sofia, Bulgaria.
Drenska
A
A
Gorantcheva
J
J
Tyutyulkova
N
N
Vlahov
V
V
D000107:Acetylation; D000328:Adult; D000983:Antipyrine / Q000493:pharmacokinetics; D001682:Biological Availability; D002031:Bulgaria; D002110:Caffeine / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004177:Dipyrone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D013810:Therapeutic Equivalency
D002110:Caffeine; D004177:Dipyrone; D000983:Antipyrine