Pharmacokinetic/pharmacodynamic approach to assess irrelevant plasma or urine drug concentrations in postcompetition samples for drug control in the horse.
The current performance of analytical techniques used for drug control in horses lead the Regulatory Authorities to decide whether trace levels of drugs legitimately used for therapeutic medication should or should not be reported. Here, we propose a well-ordered and nonexperimental pharmacokinetic/pharmacodynamic approach for the determination of irrelevant drug plasma (IPC) and urine concentrations (IUC). The published plasma clearance is used to transform an effective (marketed) dose into an effective concentration (EPC). EPC is transformed into an IPC by applying a safety factor (SF). This method is based on several assumptions (eg, drug effects reversibly driven by plasma concentration, linearity of drug disposition). The suitability of the computed IPC and IUC can be checked by calculating the residual amount of drug at IPC and computing a minimal drug withdrawal time. It is concluded that controlling the drug effect (using drug or any analyte concentration as a marker) rather than the drug exposure will be more demanding and also makes urine a less than ideal matrix.
Toutain
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PL
UMR 181 INRA/ENVT Physiopathologie et Toxicologie Expérimentales, Ecole Nationale Vétérinaire de Toulouse, France.
Lassourd
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V
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D004300:Doping in Sports; D016903:Drug Monitoring / Q000379:methods / Q000662:veterinary*; D004350:Drug Residues / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D006736:Horses / Q000097:blood* / Q000652:urine*; D008657:Metabolic Clearance Rate; D009043:Motor Activity / Q000187:drug effects; D010653:Phenylbutazone / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D010805:Physical Conditioning, Animal / Q000379:methods / Q000502:physiology; D012449:Safety; D019155:Veterinary Drugs / Q000097:blood* / Q000652:urine*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D019155:Veterinary Drugs; D010653:Phenylbutazone