G. Heinemeyer et al., THE KINETICS OF METAMIZOL AND ITS METABOLITES IN CRITICAL-CARE PATIENTS WITH ACUTE RENAL DYSFUNCTION, European Journal of Clinical Pharmacology, 45(5), 1993, pp. 445-450
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.