THE KINETICS OF METAMIZOL AND ITS METABOLITES IN CRITICAL-CARE PATIENTS WITH ACUTE RENAL DYSFUNCTION

We have studied the clearance of monomethylaminoantipyrine (MMAAP), th e pharmacologically active form of metamizol, in 46 patients in surgic al intensive care with different degrees of renal dysfunction. In 23 p atients without any renal impairment, mean clearance was 2.8 ml . min- 1. kg-1. Twentyone patients with acute renal impairment had a signific antly reduced clearance of MMAAP (0.83 ml . min-1 . kg-1). There was a lso reduced clearance in four patients with septic shock (1.0 ml min-1 . kg-1). Kinetics of the metabolites of MMAAP (N-formylaminoantipyrin e (FAAP), aminoantipyrine (AAP), and its secondary product N-acetylami noantipyrine (AcAAP)) were calculated. FAAP and AcAAP showed delayed i nvasion, which can be explained by reduced hepatic metabolic activity. The product of N-demethylation, AAP, was not significantly altered. T he delayed elimination of monomethylaminoantipyrine can be explained b y reduced hepatic function in parallel with acute renal failure due to disturbed cardiovascular function caused by septic shock. This may al so lead to disturbed hepatic macro- and microperfusion associated with altered oxygen supply and oxygen consumption.