ABSTRACT
BACKGROUND: Repeated topical application of indomethacin is common in Japanese racehorses, despite the lack of pharmacokinetic data. OBJECTIVES: To determine the concentrations of indomethacin and its metabolite, desmethylindomethacin, in plasma and urine of Thoroughbreds topically treated repeatedly with indomethacin. STUDY DESIGN: In vivo experimental. METHODS: Seven female Thoroughbreds were topically treated with 50 g of 1% indomethacin cream per horse to the back and hips (500 mg of indomethacin/head/2400 cm2 , 0.21 g/cm2 ) for 3 consecutive days. Samples were pretreated by protein precipitation for plasma and liquid-liquid extraction with ethyl acetate after hydrolysis with hydrochloric acid for urine. The concentrations of indomethacin and desmethylindomethacin in plasma and urine were measured by liquid chromatography-mass spectrometry. RESULTS: Indomethacin was quantifiable in plasma up to 48-72 h and in urine up to 96 h after the final application. Desmethylindomethacin was quantifiable in plasma up to 48 h and in urine up to 72-96 h after the final application. MAIN LIMITATIONS: The relationship between the local and systemic indomethacin concentrations after the topical application was not clarified. CONCLUSIONS: Pharmacokinetic data were acquired for repeated topical administration of 1% indomethacin cream to Thoroughbreds. Hydrolysing urine samples with hydrochloric acid was effective for the analysis of indomethacin and its metabolite, and indomethacin may be an excellent marker analyte for doping tests. The estimated withdrawal time based on the limit of detection was 342 h.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Horses/blood , Indomethacin/pharmacokinetics , Administration, Topical , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/blood , Anti-Inflammatory Agents, Non-Steroidal/urine , Area Under Curve , Drug Administration Schedule , Female , Half-Life , Horses/urine , Indomethacin/administration & dosage , Indomethacin/blood , Indomethacin/urineABSTRACT
Procaterol (PCR) is a beta-2-adrenergic bronchodilator widely used in Japanese racehorses for treating lower respiratory disease. The pharmacokinetics of PCR following single intravenous (0.5 µg/kg) and oral (2.0 µg/kg) administrations were investigated in six thoroughbred horses. Plasma and urine concentrations of PCR were measured using liquid chromatography-mass spectrometry. Plasma PCR concentration following intravenous administration showed a biphasic elimination pattern. The systemic clearance was 0.47 ± 0.16 L/h/kg, the steady-state volume of the distribution was 1.21 ± 0.23 L/kg, and the elimination half-life was 2.85 ± 1.35 h. Heart rate rapidly increased after intravenous administration and gradually decreased thereafter. A strong correlation between heart rate and plasma concentration of PCR was observed. Plasma concentrations of PCR after oral administration were not quantifiable in all horses. Urine concentrations of PCR following intravenous and oral administrations were quantified in all horses until 32 h after administration. Urine PCR concentrations were not significantly different on and after 24 h between intravenous and oral administrations. These results suggest that the bioavailability of orally administrated PCR in horses is very poor, and the drug was eliminated from the body slowly based on urinary concentrations. This report is the first study to demonstrate the pharmacokinetic character of PCR in thoroughbred horses.
