Medication control of flunixin in racing horses: Possible detection times using Monte Carlo simulations

Autor: Kanichi Kusano, Fumio Sato, Masayuki Yamada, Kentaro Fukuda, Yohei Minamijima, Taisuke Kuroda, Pierre-Louis Toutain, Shun-ichi Nagata, Shozo Yamashita, Atsutoshi Kuwano, Norihisa Tamura, Hiroshi Mita, Motoi Nomura
Rok vydání: 2021
Předmět:
Zdroj: Equine Veterinary Journal. 54:979-988
ISSN: 2042-3306
0425-1644
DOI: 10.1111/evj.13532
Popis: Background For medication control in several jurisdictions, withdrawal time is the period of refrain from racing after drug administration. It is set by adding a safety period to an experimental detection time. However, there are no reports of statistical analyses of detection time for the determination of withdrawal time in flunixin meglumine-treated horses. Objective To analyse the population pharmacokinetics of flunixin in horses through the generation of a dataset for detection time statistical analysis and predictions via Monte Carlo simulation. Study design Experimental study. Methods Drug plasma and urine concentrations following single intravenous (i.v.) administration of flunixin 1.1 mg/kg bodyweight (BW) in 10 horses and multiple administration of q 24 h for 5 days in 10 horses were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Data were modelled using a nonlinear mixed effect model followed by Monte Carlo simulation. Irrelevant plasma concentration (IPC) and irrelevant urine concentration (IUC) were calculated using the Toutain approach. Detection times were obtained considering the time after the last administration for selected quantiles of 5000 hypothetical horses under the International Screening Limit (ISL) proposed by the International Federation of Horseracing Authorities (plasma: 1 ng/ml, urine; 100 ng/ml) RESULTS: For a regimen of 1.1 mg/kg BW q 24 h, the IPC and IUC values were 2.0 and 73.0 ng/ml, respectively. Detection times in plasma above the ISL for 90% of simulated horses were estimated as 74 h after a single 1.1 mg/kg dose administration, 149 h and 199 h after multiple doses over 5 days at either 24- or 12-h intervals, respectively. Corresponding detection times in urine were 46 h, 68 h and 104 h, respectively. Main limitation Only female horses were investigated. Conclusions Statistical detection times for different flunixin meglumine regimens indicated a delay of detection time in plasma after multiple administrations under ISL.
Databáze: OpenAIRE
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