PHARMACOKINETICS OF INTRAVENOUS AND ORAL PRETHCAMIDE IN HORSES

The respiratory stimulant prethcamide is a mixture of equal parts of c rotethamide and cropropamide. A specific and sensitive gas chromatogra phic method for the determination of crotethamide and cropropamide in horse plasma and urine is described. Both components of prethcamide we re extracted from plasma and urine into dichloromethane. The extracts were analyzed by capillary gas chromatography with thermionic detectio n in the nitrogen-specific detection mode. The lower limits of quantit ation were 4.0 ng ml(-1) of plasma and 10.0 ng ml(-1) of urine. Calibr ation curves were linear from 2.0-100 ng ml(-1) of plasma for both com ponents, Pharmacokinetic parameters for crotethamide and cropropamide after intravenous and oral dosing were estimated by analysis of plasma concentration versus rime data. The total plasma clearance of croprop amide was greater than that of crotethamide and both values were great er than 5 ml min(-1) kg(-1). Renal clearance values of the two drugs w ere comparable and were much less than estimates of filtration clearan ce values in horses, indicating extensive re-absorption of both compon ents from the renal tubules. Both compounds were metabolized by N-deme thylation of the [(dimethylamino)-carbonyl]-propyl moiety and these me tabolites were excreted in urine. The method was demonstrated to be su itable for detecting illicit administration of prethcamide to competit ion horses.