Pharmacokinetics of intravenous and oral prethcamide in horses

The respiratory stimulant prethcamide is a mixture of equal parts of crotethamide and cropropamide. A specific and sensitive gas chromatographic method for the determination of crotethamide and cropropamide in horse plasma and urine is described. Both components of prethcamide were extracted from plasma and urine into dichloromethane. The extracts were analyzed by capillary gas chromatography with thermionic detection in the nitrogen-specific detection mode. The lower limits of quantitation were 4.0 ng ml-1 of plasma and 10.0 ng ml-1 of urine. Calibration curves were linear from 2.0-100 ng ml-1 of plasma for both components. Pharmacokinetic parameters for crotethamide and cropropamide after intravenous and oral dosing were estimated by analysis of plasma concentration versus time data. The total plasma clearance of cropropamide was greater than that of crotethamide and both values were greater than 5 ml min-1 kg-1. Renal clearance values of the two drugs were comparable and were much less than estimates of filtration clearance values in horses, indicating extensive re-absorption of both components from the renal tubules. Both compounds were metabolized by N-demethylation of the [(dimethylamino)-carbonyl]-propyl moiety and these metabolites were excreted in urine. The method was demonstrated to be suitable for detecting illicit administration of prethcamide to competition horses.