Wang Z Y, Stern I J
Drug Metab Dispos. 1975 Nov-Dec;3(6):536-42.
A polyoxypropylene-polyoxyethylene block copolymer of about 4750 daltons (Poloxamer 108, Pluronic F-38) used in a new protein fractionation procedure may be infused into patients receiving therapeutic plasma fractions. We studied the disposition and pharmacokinetics of Poloxamer 108 in rats as an initial step towards understanding its behavior in man. After iv administration in rats, about 94% of 7 or 100 mg/kg doses of ethylene-14C-labeled polymer was excreted in the urine in 3 days. About 6% of the label appeared in feces. Erythrocyte membranes were not permeable to the polymer, and only the parent compound was demonstrable in urine. Twenty hours after dosing, small residues were detectable only in the kidney, liver, small intestine, and carcass. The third phase of the plasma disappearance pattern was evident only at the larger dose, but plasma disappearance kinetics were independent of the dose in the range used here. Thus, most of poloxamer 108 was eliminated rapidly in rats by renal excretion, and a smaller portion probably was removed by biliary excretion. These results will be applied to continuing studies of Poloxamer 108 disposition in man.
一种用于新的蛋白质分离程序的约4750道尔顿的聚氧丙烯-聚氧乙烯嵌段共聚物（泊洛沙姆108，普朗尼克F-38）可注入接受治疗性血浆成分的患者体内。作为了解其在人体中行为的第一步，我们研究了泊洛沙姆108在大鼠体内的处置和药代动力学。在大鼠静脉给药后，7或100mg/kg剂量的乙烯-14C标记聚合物中约94%在3天内随尿液排出。约6%的标记物出现在粪便中。红细胞膜对该聚合物不渗透，尿液中仅可检测到母体化合物。给药20小时后，仅在肾脏、肝脏、小肠和尸体中可检测到少量残留物。血浆消失模式的第三阶段仅在较大剂量时明显，但血浆消失动力学在此处使用的剂量范围内与剂量无关。因此，泊洛沙姆108在大鼠体内大部分通过肾脏排泄迅速消除，一小部分可能通过胆汁排泄清除。这些结果将应用于对泊洛沙姆108在人体处置的持续研究。
