THE METABOLIC CONVERSION OF METAMIZOLE (DIPYRONE) IN MALE AND FEMALE PATIENTS AFTER TOTAL GASTRECTOMY FOR STOMACH CANCER

Metamizole (dipyrone) is a non-opioid analgesic drug used to treat postoperative pain. The pharmacological activity of metamizole is determined by two metabolites: N-methyl-4-aminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The conversion of metamizole to metabolites may be impaired in patients who underwent total gastrectomy due to pathophysiological lesions. Moreover, there may be differences in the metabolism of metamizole between men and women. The aim of the research was to analyze the pharmacokinetics of 4-MAA and 4-AA in patients after total gastrectomy, allowing for their sex. The research was carried out on patients with Roux-en-Y reconstruction after gastrectomy. Male (n = 25) and female patients (n = 13) received a single oral dose of 500 mg of metamizole. The plasma concentrations of 4-MAA and 4-AA were measured with high-pressure liquid chromatography with UV detection. The AUC(o-t) of 4-MAA in the female group was higher than in the male group (22.90 +/- 17.65 vs. 15.37 +/- 15.12 mu gxh/mL), but the difference was not statistically significant (p = 0.0561). The AUC(4-AA)/AUC(4-MAA) and Cmax.4-AA/C(m)(ax)(,4--MAA )ratios in the male and female groups were comparable (p = 0.2464 and p = 0.7441, respectively). The greater exposure of the women after gastrectomy to the more potent metabolite 4-MAA may indicate that the analgesic therapy was more effective than in the men. The lack of statistically significant differences in the values of C-m(ax),4-AA/C(max)(,4)(-MAA )and AUC(4-AA)/AUC(4-)(AA) indirectly indicates that there were no sex-dependent changes in the demethylation of metamizole.