THE PHARMACOKINETICS OF THE DIPYRONE PRODUCT 4-METHYLAMINOANTIPYRINE IN PATIENTS WITH LIVER-CIRRHOSIS

Dipyrone (noramidopyrine methanesulphonate) is a drug with analgesic, antipyretic and anti-inflammatory properties. It is hydrolysed in the gastrointestinal tract to an active moiety, methylaminoantipyrine (MAA), which is subsequently absorbed. The pharmacokinetic properties of MAA were determined following the administration of a single oral Ig dose of dipyrone to 10 patients with liver cirrhosis, and compared with those obtained in 12 healthy subjects. The mean maximum plasma MAA concentration did not differ between the 2 groups. Significant differences (p < 0.05) were found between cirrhotic patients and healthy subjects in the mean (+/- SEM) time to reach peak concentration (3.1 +/- 0.7 vs 1.6 +/- 0.1h, respectively), elimination half-life (9.6 +/- 1.6 vs 2.7 +/- 0.2h), apparent volume of distribution (0.83 +/- 0.14 vs 0.58 +/- 0.03 L/kg), total plasma clearance (1.48 +/- 0.48 vs 2.68 +/- 0.23 ml/min/kg), renal clearance (0.062 +/- 0.013 vs 0.100 +/- 0.013 ml/min/kg), nonrenal clearance (0.95 +/- 0.18 vs 2.58 +/- 0.22 ml/min/kg), and the amount of MAA in the urine (191.3 +/- 35.2 vs 104.9 +/- 9.4-mu-mol). Significant correlations were found in the cirrhotic patients between the mean MAA elimination half-life and serum bilirubin levels (r = 0.73), prothrombin time (r = 0.57) and serum albumin (r = -0.69). There was no consistent correlation between any of the pharmacokinetic parameters and serum enzyme levels. Whether in practice pharmacokinetic alterations of MAA in patients with liver cirrhosis necessitate dose-adjustment or translate into a more prolonged analgesic-antipyretic action of dipyrone remains to be determined.