Gayrard V, Alvinerie M, Toutain P L
Ecole Nationale Vétérinaire de Toulouse, Unité associée INRA de Physiopathologie et Toxicologie expérimentales, France.
Vet Parasitol. 1999 Feb 1;81(1):47-55. doi: 10.1016/s0304-4017(98)00236-2.
The plasma pharmacokinetics of doramectin and invermectin after topical administration (500 microg kg(-1)) were compared over a 50-day period in 24 young beef cattle. Observed maximum concentration (Cmax) and time to maximum concentration (Tmax) were determined directly from plasma concentrations for each animal. The area under the plasma concentration-time curve (AUC) and mean residence time (MRT) were calculated as indices of drug exposure and persistence. The Cmax of doramectin (12.2+/-4.8 ng ml(-1)) and ivermectin (12.2+/-6.0 ng ml(-1)) and Tmax of doramectin (4.3+/-1.6 days) and ivermectin (3.4+/-0.8 days) were not significantly different (p > 0.05). In contrast, the AUC of doramectin (168.0+/-41.7 ng day ml(-1)) was significantly greater than that of ivermectin (115.5+/-43.0 ng day ml(-1)). Furthermore, the range of AUC values calculated for ivermectin was wider than that obtained for doramectin, extending from 51.3 to 182.3 ng day ml(-1) for ivermectin versus 104.3-228.7 ng day ml(-1) for doramectin. The MRT was significantly greater for doramectin (12.8+/-1.9 days) than for ivermectin (8.4+/-1.5 days). It was concluded that a 500 microg kg(-1) pour-on administration of doramectin and ivermectin led to an overall exposure as reflected by the mean AUC, that was 45% higher for doramectin compared to ivermectin and that the relative inter-individual variability was less for doramectin than for ivermectin. Possible therapeutic consequences of these differences between doramectin and ivermectin pour-on formulations are discussed.
在24头年轻肉牛中，对多拉菌素和伊维菌素经皮给药（500微克/千克）后的血浆药代动力学进行了为期50天的比较。直接从每头动物的血浆浓度中确定观察到的最大浓度（Cmax）和达到最大浓度的时间（Tmax）。计算血浆浓度-时间曲线下面积（AUC）和平均驻留时间（MRT）作为药物暴露和持久性的指标。多拉菌素的Cmax（12.2±4.8纳克/毫升）和伊维菌素的Cmax（12.2±6.0纳克/毫升）以及多拉菌素的Tmax（4.3±1.6天）和伊维菌素的Tmax（3.4±0.8天）无显著差异（p>0.05）。相比之下，多拉菌素的AUC（168.0±41.7纳克·天/毫升）显著高于伊维菌素的AUC（115.5±43.0纳克·天/毫升）。此外，伊维菌素计算得到的AUC值范围比多拉菌素的更宽，伊维菌素的范围为51.3至182.3纳克·天/毫升，而多拉菌素为104.3 - 228.7纳克·天/毫升。多拉菌素的MRT（12.8±1.9天）显著长于伊维菌素的MRT（8.4±1.5天）。得出的结论是，500微克/千克的多拉菌素和伊维菌素浇泼剂给药导致的总体暴露（以平均AUC反映），多拉菌素比伊维菌素高45%，且多拉菌素的个体间相对变异性小于伊维菌素。讨论了多拉菌素和伊维菌素浇泼剂制剂之间这些差异可能产生的治疗后果。
