COMPARATIVE BIOAVAILABILITY OF 2 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) wa s compared after oral administration of a test (Analgin(R)) and a refe rence formulation, both containing 1 g of metamizole. The study was co nducted in 12 healthy volunteers according to an open, randomized, cro ss-over design. The geometric mean of the area under the serum concent ration-time curves (AUC) of 4-MAA for the test formulation was 87.61 ( 57.58-133.30) mu g . h/ml and was similar to that for the reference fo rmulation (86.83; 53.86-139.92 mu g . h/ml). No statistically signific ant differences between test and reference formulation were found with respect to the rate of absorption (C-max, t(max), 100 C-max/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 d ifferences were found between slow and rapid acetylators in the bioava ilability of 4-MAA, the pharmacologically active metabolite of metamiz ole.