Lin C, Gupta S, Loebenberg D, Cayen M N
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA.
Antimicrob Agents Chemother. 2000 Apr;44(4):916-9. doi: 10.1128/AAC.44.4.916-919.2000.
The pharmacokinetics of SCH 27899, a novel oligosaccharide compound of the everninomicin class with excellent activity against gram-positive strains, was studied with mice, rats, rabbits, and cynomolgus monkeys following intravenous administration as SCH 27899-N-methylglucamine-hydroxypropyl beta-cyclodextrin. Concentrations of SCH 27899 in mouse serum, rat plasma, and rabbit serum were determined by a high-pressure liquid chromatography method on a poly(styrene-divinyl benzene) column, and those in monkey plasma were determined by a paired-ion chromatographic method. Plasma and serum concentrations of SCH 27899 exhibited a biexponential decline in all species following intravenous administration. The half-lives at beta phase were 3.0 to 7.9 h in mice, rats, and rabbits and 24 h in cynomolgus monkeys. There was a linear relationship between the area under the curve extrapolated to infinity [AUC(I)] in mice and dose. Rabbits also exhibited dose proportionality in AUC(I). However, in rats, increasing the dose from 3 to 60 mg/kg of body weight resulted in a 49-fold increase in AUC(I). When the species was changed from mouse to rat, rabbit, or cynomolgus monkey, AUC(I) increased, whereas clearance (CL) decreased. It was concluded that the pharmacokinetics of SCH 27899 in animals varied with species; CL was the highest in mice and rats, followed by rabbits and cynomolgus monkeys.
SCH 27899是一种新的寡糖化合物，属于埃弗米星类，对革兰氏阳性菌株具有优异活性。以SCH 27899-N-甲基葡糖胺-羟丙基β-环糊精的形式对小鼠、大鼠、兔子和食蟹猴进行静脉给药后，研究了其药代动力学。采用高压液相色谱法在聚（苯乙烯-二乙烯基苯）柱上测定小鼠血清、大鼠血浆和兔子血清中SCH 27899的浓度，采用配对离子色谱法测定猴血浆中SCH 27899的浓度。静脉给药后，所有物种的血浆和血清中SCH 27899浓度均呈双指数下降。小鼠、大鼠和兔子β相的半衰期为3.0至7.9小时，食蟹猴为24小时。小鼠曲线下面积外推至无穷大[AUC(I)]与剂量之间呈线性关系。兔子的AUC(I)也呈剂量比例关系。然而，在大鼠中，将体重剂量从3毫克/千克增加到60毫克/千克会导致AUC(I)增加49倍。当物种从小鼠变为大鼠、兔子或食蟹猴时，AUC(I)增加，而清除率(CL)降低。得出结论，SCH 27899在动物中的药代动力学因物种而异；CL在小鼠和大鼠中最高，其次是兔子和食蟹猴。
