Pharmacokinetics of intravenous and oral prethcamide in horses.
Abstract: 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.
Publication Date: 1997-02-01 PubMed ID: 9127276DOI: 10.1016/s0731-7085(96)01885-7Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the breakdown and absorption process (pharmacokinetics) of prethcamide, a respiratory stimulant, when given to horses intravenously and orally. Prethcamide is a combination of crotethamide and cropropamide. The study also establishes a way of detecting the illicit use of prethcamide in competitive horses.
Method Development
- The researchers developed a precise and sensitive gas chromatographic method for measuring the levels of prethcamide’s two components in horse plasma and urine.
- They extracted crotethamide and cropropamide from horse plasma and urine with dichloromethane.
- After extraction, the samples were analyzed using capillary gas chromatography with thermionic detection in nitrogen-specific mode.
- The lowest amount of each component that this method could quantify was 4.0 nanograms per milliliter (ng/ml) of plasma and 10.0 ng/ml of urine.
- The calibration curves for both components were linear within a range of 2.0 to 100 ng/ml of plasma.
Analysis of Pharmacokinetics
- After the administration of prethcamide orally and intravenously, the researchers analytically estimated the pharmacokinetics by analyzing the plasma concentration vs. time data for both crotethamide and cropropamide.
- It was found that the total plasma clearance rate of cropropamide was higher than that of crotethamide.
- Both rates were found to exceed 5 milliliters per minute per kilogram (ml/min/kg).
- The renal clearance values were observed to be similar for both components, indicating sweeping reabsorption from the renal tubules because the estimated values were much less than filtration clearance values in horses.
Metabolism and Detection
- Both crotethamide and cropropamide are metabolized by N-demethylation of a particular moiety.
- The metabolites are then disposed of through the horse’s urine.
- The developed method has been shown to be effective in detecting prohibited use of prethcamide in racehorses.
Cite This Article
APA
Sams RA, Gerken DF, Ashcraft SM.
(1997).
Pharmacokinetics of intravenous and oral prethcamide in horses.
J Pharm Biomed Anal, 15(5), 639-651.
https://doi.org/10.1016/s0731-7085(96)01885-7 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Ohio State University, Columbus 43210, USA.
MeSH Terms
- Administration, Oral
- Aminobutyrates / blood
- Aminobutyrates / pharmacokinetics
- Aminobutyrates / urine
- Animals
- Blood Proteins / metabolism
- Chromatography, Gas
- Crotonates / blood
- Crotonates / pharmacokinetics
- Crotonates / urine
- Female
- Horses / blood
- Horses / metabolism
- Horses / urine
- Injections, Intravenous
- Protein Binding
Citations
This article has been cited 1 times.- Docherty JR. Pharmacology of stimulants prohibited by the World Anti-Doping Agency (WADA). Br J Pharmacol 2008 Jun;154(3):606-22.
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