盐酸三环哌酯在小鼠体内的药代动力学

目的研究抗胆碱新药盐酸三环哌酯（ＴＣＰＮ）在小鼠体内的药代动力学及组织分布。方法药代动力学采用放射受体分析法研究，组织中的分布用放射同位素分析法研究。结果小鼠ｓｃＴＣＰＮ后，血液中药物浓度的经时过程符合一级吸收二室模型（Ｔ１／２β为２．２８ｈ，Ｔｍａｘ为０．１２５ｈ，Ｃｍａｘ为３．４４μｇ·Ｌ－１，Ｃｌ为２３．０Ｌ·ｋｇ－１·ｈ－１）。小鼠ｓｃ［３Ｈ］－ＴＣＰＮ后，分布高峰放射性依次为肾＞肝＞脑＞颌下腺＞肠１９９８－０４－０３收稿，１９９８－０７－２６修回＊国家自然科学基金资助课题，Ｎｏ３９１３００９０－２作者简介：葛召恒，男，３２岁，硕士，助理研究员；阮金秀，男，６２岁，研究员，博士生导师，中国毒理学会副理事长，中国药理学会药物代谢专业委员会主任委员＞心＞肌肉，唯有脑组织的放射性以较高的水平维持较长的时间。预先给小鼠ｓｃ不同剂量的ＱＮＢ，可不同程度地降低脑中放射性的分布。结论ＴＣＰＮ从血中的消除较快，但在脑组织分布时间长，这与药物与脑中Ｍ受体的特异性结合有关。

Pharmacokinetics of tricyclopinate hydrochloride in mice

AIM To study the pharmacokinetics and tissue distribution of tricyclopinate hydrochloride (TCPN, a new antichlolinergic drug) in mice. METHODS The pharmacokinetics of TCPN and the tissue distribution of TCPN was studied with radioreceptor assay and radioactive isotope assay respectively. RESULTS The concentration time curve after sc 50 μg·kg -1 of TCPN was fitted to first order absorption two compartment model: with 2 28 h of T 12β 0 125 h of T max , 3 44 μg·L -1 of C max and 23 0 L·kg -1 ·h -1 of Cl. After sc 50 μg·kg -1 of TCPN,the gradient of peak radioactivity in the tissues was kidney>liver>brain>submandibular glands>colon>heart>skeletal muscle. As compared with the other tissues, the redioactivity in brain remained at a higher level with a longer eliminating time and obviously decreased after sc QNB. CONCLUSIONS That TCPN eliminated rapidly in blood but slowly in brain was related to the binding of TCPN to muscarinic acetylcholine receptors in brain.