Distribution and excretion of [14C]-labelled [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]- [2'-14C]-acetic acid in rats.
A non-redox dual inhibitor of both cyclooxygenase and 5-lipoxygenase, [2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5- yl]-[2'-14C]-acetic acid (3, ML 3000), was synthesized as [14C]-labelled compound and administered orally to rats. Distribution of radioactivity was examined by use of whole-body autoradiography after administration of doses in the range 13.7-26.6 mg/kg. Highest tissue levels were detected in the lung, liver, kidney, heart and large and small intestine. 48 h after administration, 58.3% of the total radioactivity was found in the feces and 7.9% in the urine. The distribution of radioactivity in the tissue, time course of plasma concentration, urinary and fecal excretion as well as hydrolysis experiments with beta-glucuronidase suggest an enterohepatic circulation and metabolization to glucuronides.
Deigner
H P
HP
Pharmazeutisch-Chemisches Institut der Universität Heidelberg, Germany.
Freyberg
C E
CE
Laufer
S
S
D000085:Acetates / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D005260:Female; D007553:Isotope Labeling; D016859:Lipoxygenase Inhibitors / Q000493:pharmacokinetics* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D011758:Pyrroles / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D000085:Acetates; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; C088092:licofelone