[Renal elimination and metabolism of etofenamate in volunteers after administration of various doses].
Renal Elimination and Metabolism of Etofenamate after Intramuscular Administration of Different Doses to volunteers. Renal elimination of etofenamate (active substance of Rheumon i.m.) after i.m. injection of oily solution of etofenamate to volunteers was investigated by HPTLC and GC. After injection of 250, 500 and 1000 mg etofenamate, free and conjugated flufenamic acid (flu), 5-hydroxy- and 4'-hydroxy flufenamic acid (5-OH-flu, 4'-OH-flu) were found as main metabolites in urine. Besides that several minor metabolites were identified. The ratio of free to conjugated metabolites was 1:10 to 1:25. From the doses administered 30% were eliminated as main metabolites. Overall amounts (in mg) of the eliminated metabolites and the doses correlated with each other (r = 0.9334), whereas the percent ratio of 5-OH-flu and of 4'-OH-flu increased with dose. Half lives of renal elimination for flu, 5-OH-flu and 4'-OH-flu are largely independent of dose. The half life of flufenamic acid corresponds roughly to data from plasma levels (7-9 h), the two hydroxy derivatives are eliminated into urine with half lives from 15 to 24 h. The results show, that i.m. injection of an oily etofenamate solution follows a linear dose independent kinetic, while the amounts absorbed and renally eliminated are proportional to dose. The results correspond to plasma level studies.
Dell
H D
HD
Biochemischen Abteilung der Troponwerke GmbH & Co. KG, Köln.
Beckermann
B
B
Fiedler
J
J
Kamp
R
R
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D005439:Flufenamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000652:urine; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007668:Kidney / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D009821:Oils; D014677:Pharmaceutical Vehicles
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009821:Oils; D014677:Pharmaceutical Vehicles; D005439:Flufenamic Acid; C015207:etofenamate
Renale Elimination und Metabolismus von Etofenamat bei Probanden nach intramuskulärer Applikation verschiedener Dosen.