Duthu G S
J Pharm Sci. 1985 Sep;74(9):943-6. doi: 10.1002/jps.2600740907.
Knowledge of the disposition of macrolides in a single animal species has been insufficient for the prediction of the pharmacokinetics of macrolides in humans. To better understand the species differences in the pharmacokinetics of macrolide antibiotics, the disposition of erythromycin, oleandomycin, and tylosin in several mammalian species was examined. Generally, the serum concentration versus time profiles of these drugs after intravenous administration were described by two-compartment kinetic models and were similar within each species. These drugs were rapidly cleared, resulting in terminal half-lives of less than 2 h. Comparison of their pharmacokinetics showed greater variation in antibiotic disposition among animal species than noted for the differences within a species. When the pharmacokinetic data was fitted to an allometric model, the logarithms of volume of distribution, clearance, and half-life were linearly related to the logarithms of body weight. From these relationships, the human pharmacokinetics of erythromycin and oleandomycin were extrapolated and found to approximate observed human pharmacokinetics.
仅了解大环内酯类药物在单一动物物种中的处置情况，不足以预测其在人体内的药代动力学。为了更好地理解大环内酯类抗生素药代动力学的物种差异，研究人员考察了红霉素、竹桃霉素和泰乐菌素在几种哺乳动物物种中的处置情况。一般来说，这些药物静脉给药后的血清浓度-时间曲线可用二室动力学模型描述，且在每个物种内相似。这些药物清除迅速，导致终末半衰期小于2小时。比较它们的药代动力学发现，动物物种之间抗生素处置的差异比同一物种内的差异更大。当药代动力学数据拟合到异速生长模型时，分布容积、清除率和半衰期的对数与体重的对数呈线性相关。根据这些关系，外推了红霉素和竹桃霉素的人体药代动力学，发现其与观察到的人体药代动力学相近。
