Polymorphic 2-hydroxylation of desipramine |
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| Authors: | M-L Dahl L Iselius C Alm J-O Svensson D Lee I Johansson M Ingelman-Sundberg F Sjöqvist |
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| Institution: | (1) Institute of Clinical Pharmacology, Klinikum Steglitz, Free University of Berlin, Germany;(2) Clinic of Operative Intensive Care Medicine, Klinikum Steglitz, Free University of Berlin, Germany;(3) Krankenhaus Moabit, Berlin, Germany;(4) Present address: Bundesgesundheitsamt, Thielallee 88–92, D-14195 Berlin, Germany;(5) Present address: Institut für Klinische Pharmakologie, Charité, Humboldt Universität, D-10098 Berlin, Germany;(6) Present address: Krankenhaus Nordwest, D-60488 Frankfurt/Main, Germany |
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| Abstract: | Summary We have studied the clearance of monomethylaminoantipyrine (MMAAP), the pharmacologically active form of metamizol, in 46 patients in surgical intensive care with different degrees of renal dysfunction.In 23 patients without any renal impairment, mean clearance was 2.8 ml·min–1·kg–1. Twentyone patients with acute renal impairment had a significantly reduced clearance of MMAAP (0.83 ml·min–1·kg–1). There was also reduced clearance in four patients with septic shock (1.0 ml·min–1·kg–1).Kinetics of the metabolites of MMAAP (N-formylaminoantipyrine (FAAP), aminoantipyrine (AAP), and its secondary product N-acetylaminoantipyrine (AcAAP)) were calculated. FAAP and AcAAP showed delayed invasion, which can be explained by reduced hepatic metabolic activity. The product of N-demethylation, AAP, was not significantly altered.The delayed elimination of monomethylaminoantipyrine can be explained by reduced hepatic function in parallel with acute renal failure due to disturbed cardiovascular function caused by septic shock. This may also lead to disturbed hepatic macro- and microperfusion associated with altered oxygen supply and oxygen consumption. |
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| Keywords: | Metamizol Acute renal failure Sepsis intensive care patients drug metabolism |
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