Facultad de Medicina Veterinaria, Universidad de Concepción, Chillán, Chile.
Vet Parasitol. 2010 May 28;170(1-2):112-9. doi: 10.1016/j.vetpar.2010.01.038. Epub 2010 Feb 4.
A study was done to compare plasma disposition kinetics and the fecal elimination profile of doramectin (DRM) after oral or intramuscular (IM) administration in horses. Ten clinically healthy horses, 328-502 kg body weight (bw), were assigned to 2 experimental groups of 5 horses each. Group 1 was treated with an oral dose of 0.2 mg DRM/kg bw, while Group 2 was treated with 0.2 mg DRM/kg bw by IM route. Blood and fecal samples were collected at different times between 0.5h and 60 days post-treatment. After plasma and fecal drug extraction and derivatization, samples were analysed by high performance liquid chromatography (HPLC). A non-compartmental kinetic analysis was performed. Results were expressed as mean+/-standard deviation and were compared using Mann-Whitney U-test. The parent molecule was detected in plasma between 30 min and either 30 (oral) or 60 (IM) days post-treatment. Peak plasma concentrations (C(max)) of 51.6+/-22.2 and 33.3+/-10.5 ng/mL were obtained after oral administration and IM route, respectively. Differences between administration route were not statistically significant (P=0.42). The value for the area under the concentration-time curve (AUC) was 178.6+/-53.7 and 393.6+/-66.6 ng day/mL for Group 1 and Group 2, respectively. These differences were significant (P<0.0079). The averages for mean residence time (MRT) values were 7.7+/-0.9 and 13.2+/-4.5 days for oral and IM treated groups, respectively. In horses treated using the oral route, the peak fecal concentration (F C max) was 2295+/-593 ng/g observed at 1.9+/-0.5 days after oral treatment. Whereas, for those treated by IM route, the F C max was lower (162+/-26 ng/g) (P<0.0079) and it was observed at 5.6+/-2.9 days. The results of this study showed that the administration route affects plasma disposition kinetics, bioavailability and fecal elimination of DRM.
本研究旨在比较多拉菌素（DRM）经口服或肌肉注射（IM）给药后在马体内的血浆处置动力学和粪便消除特征。将 10 匹体重为 328-502kg 的临床健康马分为 2 个实验组，每组 5 匹马。第 1 组给予 0.2mg/kg 体重的口服 DRM，第 2 组给予 0.2mg/kg 体重的 IM DRM。在治疗后 0.5 小时至 60 天的不同时间采集血样和粪便样本。在对血浆和粪便药物进行提取和衍生化后，采用高效液相色谱法（HPLC）进行分析。采用非房室动力学分析。结果以平均值±标准差表示，并采用曼-惠特尼 U 检验进行比较。在治疗后 30 分钟至 30 天（口服）或 60 天（IM）之间可在血浆中检测到母体药物。口服和 IM 途径给药后，分别获得 51.6±22.2 和 33.3±10.5ng/mL 的血浆峰浓度（C(max)）。两种给药途径之间的差异无统计学意义（P=0.42）。第 1 组和第 2 组的 AUC 值分别为 178.6±53.7 和 393.6±66.6ng·day/mL。这些差异具有统计学意义（P<0.0079）。口服和 IM 组的平均驻留时间（MRT）值分别为 7.7±0.9 和 13.2±4.5 天。口服给药的马，在口服治疗后 1.9±0.5 天达到粪便峰浓度（F C max），为 2295±593ng/g。而 IM 给药的马，F C max 较低（162±26ng/g）（P<0.0079），并在 5.6±2.9 天观察到。本研究结果表明，给药途径影响 DRM 的血浆处置动力学、生物利用度和粪便消除。
