PHARMACOKINETICS OF SCH39166 IN SUBJECTS W/ CHRONIC LIVER DISEASE

SCH39166是多巴胺D_1和D_5受体的选择性拮抗剂。所有令人上瘾的药物，甚至是美味的食物都会刺激多巴胺的神经传递。但可卡因、尼古丁、阿片剂和乙醇等药物的成瘾特性似乎与多巴胺对D1和/或D5受体的刺激有关。由于SCH39166在人体内被广泛的葡萄糖醛酸化，因此研究不同程度的肝功能改变对药物药代动力学的影响具有临床意义--特别是考虑到药物成瘾者中肝病的流行。这项单剂量研究的主要目的是评估和比较SCH39166在肝功能正常和不同程度稳定的慢性肝病患者中的药代动力学。这项研究的数据将用于为不同程度的慢性肝病患者制定剂量指南。

SCH39166 is a selective antagonist of dopamine D1 and D5 receptors. Dopamine neurotransmission is stimulated by all addictive drugs and even highly palatable food. But the addictive properties of drugs such as cocaine, nicotine, opiates and ethanol appear to be associated with dopamine stimulation of D1 and/or D5 receptors. Since SCH39166 is extensively glucuronidated in humans, it is clinically relevant to study the effects of various degrees of altered hepatic function on the pharmacokinetics of the drug -- especially in light of the prevalence of hepatic disease in substance-addicted persons. The primary objective of this single dose study is to evaluate and compare the pharmacokinetics of SCH39166 in subjects with normal liver function and with various degrees of stable chronic liver disease. Data from this study will be used to develop dosing guidelines for patients with various degrees of chronic liver disease.