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本文研究了前列腺素E1(PGE1)分别经不同途径给药后的大鼠体内药效学,旨在寻找目前PGE1注射给药的替代途径。以PGE1降压效应作为药效学指标,以静脉注射为对照,分别测定PGE1经鼻腔、舌下、肌肉(im)、腹腔(ip)给药后的药效学参数,包括峰效应时间(Tmax),血压下降最大百分数(Emax,%),效应持续时间(Td)以及血压下降百分数-时间曲线下面积(AUC,%.min)。研究结果表明,PGE1经上述途径给药后,药效学参数Emax,Td,AUC等均随给药剂量的增加而增大,提示存在明显的剂量-效应关系。根据所测Tmax值,推断上述给药途径其吸收速率的大小顺序为:鼻腔≈im>ip>舌下;依据所测药理生物利用度(PF)值,预测药物绝对生物利用度的顺序为:鼻腔>im≈ip>舌下。上述研究结果提示,PGE1经鼻腔与舌下黏膜给药,有望替代目前的注射给药。
In this paper, the pharmacokinetics of prostaglandin E1 (PGE1) in rats after different routes of administration were studied in order to search for an alternative route for the current administration of PGE1. PGE1 antihypertensive effect was used as a pharmacodynamic indicator. Pharmacodynamic parameters of PGE1 after nasal, sublingual, intramuscular and intraperitoneal (ip) administration were determined by intravenous injection. The peak effect time (Tmax ), Maximum percentage decrease in blood pressure (Emax,%), effect duration (Td), and percentage decrease in blood pressure-time under the curve of time (AUC,% .min). The results showed that, PGE1 administration by the above route, the pharmacodynamic parameters Emax, Td, AUC and so increased with the dose increased, suggesting that there is a clear dose-response relationship. According to the measured Tmax value, the order of absorption rate of the above administration routes is in the order of nasal ≈im> ip> sublingual. According to the measured pharmacological bioavailability (PF) value, the order of absolute bioavailability of drugs is predicted as follows: Nasal cavity> im≈ip> sublingual. These findings suggest that PGE1 administered via the nasal and sublingual mucosa is expected to replace the current injection.