Perfil cinético de la suxibuzona para su uso en la clínica de equidos

Abstract

Suxibuzone is a widely used non-steroidal anti-inflammatory drug in equine medicine. Chemically it is a Phenylbutazone ester. Both molecules are closely related because Suxibuzone is rapidly metabolized to Phenylbutazone when is orally or parenterally administered to the horse. The aim of this study is to evaluate the availability profile of Phenylbutazone, and its main metabolite Oxyphenbutazone, after Suxibuzone or Phenylbutazone administration at the same molecular doses, not only in fasting horses but also in animals following usual diet. Furthermore, the availability of these molecules in synovial fluid has been studied, as indicator of its ability to develop anti-inflammatory effects in the joints. In an firstly cross-over experimental phase, Suxibuzone 6.25 mg/kg (A) and Phenylbutazone 4.4 mg/kg (B) were orally administered to 19 fasting horses. Serial plasma samples were obtained and plasma and synovial fluid levels of Suxibuzone and its main active metabolites (Phenylbutazone and Oxyphenbutazone) were quantified by liquid chromatography (HPLC) using a previously validated method. Pharmacokinetic parameters were calculated using a non-compartimental analysis for all animals after both administrations. Suxibuzone was not detected in any sample. Main pharmacokinetic parameters obtained for plasma levels of Phenylbutazone were (mean ± S.D.): Tmax (h) 4.9±3.1 (A), 3.2±2.7 (B); Cmax (µg/mL) 10.2±2.2 (A), 15.5±3.6 (B); MRT0®t (h) 10.0±1.1 (A), 9.2±1.3 (B); T½(h) 7.5±1.8 (A), 7.2±1.5 (B); AUC0®t (µg.h/mL) 145.1±35.0 (A), 179.1±36.4 (B); AUC0®¥ (µg.h/mL) 172.6±44.7 (A), 206.2±45.5 (B). A relative availability of (FA/B) 0.82±0.16 was observed. Main pharmacokinetic parameters obtained for Oxyphenbutazone were (mean ± S.D.): Tmax (h) 15.3±2.8 (A), 13.8±4.8 (B); Cmax (µg/mL) 2.1±0.4 (A), 2.5±0.6 (B); MRT0®t (h) 13.5±0.9 (A), 13.1±1.0 (B); AUC0®t (µg.h/mL) 34.9±6.4 (A), 42.9±9.2 (B); FA/B 0.85±0.26. After the statistical analysis of the results obtained in this study we conclude that there are not significant differences (p Significant differences (p In a second experimental phase, the same doses of Suxibuzone (C) and Phenylbutazone (D) were administered with the usual diet, to 10 animals (5 per treatment) of the first study. Following pharmacokinetic parameters for Phenyl-butazone concentrations were obtained (mean ± S.D.): Tmax (h) 9.8±8.5 (C), 6.2±8.1 (D); Cmax (µg/mL) 7.9±3.4 (C), 9.5±1.3 (D); MRT0®24h (h) 12.1±3.6 (C), 9.0±1.9 (D); AUC0®t (µg.h/mL) 83.3±24.4 (C), 100.2±20.2 (D). For Oxyphenbutazone concentrations the values were as follows: Tmax (h) 13.6±7.9 (C), 9.8±4.0 (D); Cmax (µg/mL) 1.7±0.5 (C), 1.6±0.3 (D); MRT0®24h (h) 13.1±2.5 (C), 11.5±1.5 (D); AUC0®t (µg.h/mL) 21.6±5.1 (C), 24.3±6.6 (D). The relative availability between the same animals when the drug was administered in the fasting state or with food was FC/A 0.76±0.18 and FD/B 0.65±0.16 for Phenylbutazone concentrations; FC/A 0.74±0.20 and FD/B 0.75±0.17 for Oxyphenbutazone concentrations. A similar reduction of Phenylbutazone and Oxyphenbutazone availability was observed after both treatments when administered with food. Concentrations of Phenylbutazone and Oxyphenbutazone in synovial fluid after Suxibuzone 6.25 mg/kg in fasting animals (n=6) were after 6h: 2.3±1.4 (PBZ), 0.4±0.2 (OPBZ); after 12h: 2.6±0.7 (PBZ), 0.7±0.3 (OPBZ) and after 24h: 1.0±0.3 (PBZ), 0.7±0.2 (OPBZ). Suxibuzone concentrations in synovial fluid were not detected.

Date of Award	27 Sept 2002
Original language	Undefined/Unknown
Supervisor	Margarita Arboix Arzo (Director)