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目的考察前列腺素E_1(PGE_1)冻干脂微球在比格犬体内的药动学特征,为其临床人体用药提供参考依据。方法 24只比格犬随机分为对照组和低、中、高剂量组,每组6只,分别静脉给予参比制剂“凯时”与20、32、64μg/dog的受试制剂PGE_1冻干脂微球,于不同时间点采集血样,采用LC-MS/MS法测定比格犬体内PGE_1的血药浓度。结果比格犬静脉推注32μg/dog剂量的PGE_1冻干脂微球后,血浆中PGE1的t_(1/2)为(7.5±3.7)min,tmax为(7.6±2.9)min,Cmax为(105.0±40.4)ng/L,AUC(0~18 min)为(933.1±359.0)ng·min/L,与参比制剂“凯时”间的差异无统计学意义(P>0.05);在低、中、高3个不同剂量下,PGE1的AUC(0~18 min)、Cmax分别与剂量呈线性正相关,且性别差异无统计学意义(P>0.05)。结论 PGE_1冻干脂微球与其市售脂微球注射液“凯时”具有相同的药动学特征,不同剂量水平不影响其在比格犬体内的药动学过程。
Objective To investigate the pharmacokinetics of PGE_1 freeze-dried lipid microspheres in beagle dogs and provide a reference for its clinical use in human beings. Methods Twenty-four beagle dogs were randomly divided into control group and low, medium and high dose groups, with 6 rats in each group. The rats were administered with reference drug “Kai Shi” and 20, 32 and 64 μg / dog, respectively. PGE_1 The lipid microspheres were lyophilized and blood samples were collected at different time points. Plasma concentrations of PGE 1 in Beagle dogs were determined by LC-MS / MS. Results After Beagle dogs were intravenously injected with PGE1 at a dosage of 32μg / dog, t 1/2 of PGE1 in plasma was (7.5 ± 3.7) min, tmax was (7.6 ± 2.9) min and Cmax was ( 105.0 ± 40.4 ng / L, and the AUC of 0-18 min was (933.1 ± 359.0) ng · min / L, which was not significantly different from the reference formulation “Kai Shi” (P> 0.05). The AUC (0-18 min) and Cmax of PGE1 were linearly and dose-dependently with low, medium and high doses, respectively, with no significant difference in gender (P> 0.05). Conclusions PGE_1 freeze-dried lipid microspheres have the same pharmacokinetic characteristics as the commercially available lipid microspheres injection “Kaishi”, and different dose levels do not affect their pharmacokinetics in Beagle dogs.