Spreux-Varoquaux O, Doll J, Dutot C, Grandjean N, Cordonnier P, Pays M, Andrieu J, Advenier C
Département de Biochimie-Pharmacologie-Toxicologie, Centre Hospitalier de Versailles, Le Chesnay, France.
Br J Clin Pharmacol. 1991 Sep;32(3):399-401. doi: 10.1111/j.1365-2125.1991.tb03919.x.
The pharmacokinetics of molsidomine were investigated in six healthy volunteers and in seven patients with alcoholic cirrhosis. After a 2 mg oral dose, molsidomine elimination half-life was prolonged in cirrhotic patients (13.1 +/- 10.0 h vs 1.2 +/- 0.2 h, P less than 0.01) because of a decrease in its apparent plasma clearance (CL/F) (39.8 +/- 31.9 ml h-1 kg-1 in patients with cirrhosis vs 590 +/- 73 ml h-1 kg-1 in volunteers). The elimination half-life of the active metabolite, linsidomine (SIN-1) was also prolonged in cirrhotic patients (7.5 +/- 5.4 h vs 1.0 +/- 0.19 h, P less than 0.05). The AUC values of both molsidomine and linsidomine were increased in the cirrhotic group, but the increase in the former was considerably greater than in the latter as shown by the significant decrease of the ratio AUClinsidomine/AUCmolsidomine x 100 (4.5 +/- 6.1 in cirrhotic patients vs 23.5 +/- 3.4 in healthy volunteers, P less than 0.001). These results suggest that liver cirrhosis profoundly alters the pharmacokinetics and metabolism of molsidomine.
在6名健康志愿者和7名酒精性肝硬化患者中研究了吗多明的药代动力学。口服2mg剂量后，由于其表观血浆清除率（CL/F）降低，肝硬化患者的吗多明消除半衰期延长（13.1±10.0小时 vs 1.2±0.2小时，P<0.01）（肝硬化患者为39.8±31.9ml·h⁻¹·kg⁻¹，志愿者为590±73ml·h⁻¹·kg⁻¹）。活性代谢物林西多明（SIN-1）的消除半衰期在肝硬化患者中也延长（7.5±5.4小时 vs 1.0±0.19小时，P<0.05）。吗多明和林西多明的AUC值在肝硬化组中均升高，但前者的升高幅度明显大于后者，如AUClinsidomine/AUCmolsidomine×100的比值显著降低所示（肝硬化患者为4.5±6.1，健康志愿者为23.5±3.4，P<0.001）。这些结果表明肝硬化深刻改变了吗多明的药代动力学和代谢。
