PHARMACOKINETICS OF MIDAZOLAM FOLLOWING INTRAVENOUS AND ORAL-ADMINISTRATION IN PATIENTS WITH CHRONIC LIVER-DISEASE AND IN HEALTHY-SUBJECTS
PHARMACOKINETICS OF MIDAZOLAM FOLLOWING INTRAVENOUS AND ORAL-ADMINISTRATION IN PATIENTS WITH CHRONIC LIVER-DISEASE AND IN HEALTHY-SUBJECTS
复制标题
DOI：
10.1002/j.1552-4604.1989.tb03327.x
复制
发表时间：
1989-03-01
影响因子：
2.9
通讯作者：
CREVOISIER, C
中科院分区：
文献类型：
--
作者：
PENTIKAINEN, PJ;VALISALMI, L;CREVOISIER, C
为研究肝硬化对咪达唑仑药代动力学的影响，7名肝硬化患者和7名健康对照受试者接受咪达唑仑单次IV（7.5 mg作为碱）和p.p（15.0 mg作为碱）给药。1例腹泻患者未接受口服给药。两个研究组中咪达唑仑的分布相似，如相似的t1/2 α值所示，V1和Vss。肝硬化患者咪达唑仑的血浆蛋白结合率也无变化。咪达唑仑在患者中的消除显着延迟，表现为其较低的总清除率（3.34与5.63 ml/min/kg）、较低的总消除速率常数（0.400与0.721 h-1）和较长的消除半衰期（7.36与3.80 h）。患者口服咪达唑仑的生物利用度为76%，显著高于对照组的38%（P < 0.05）。安替比林的半衰期为32.4小时的患者和11.8小时的对照。两种药物的清除率（r = 0.680）和半衰期（r = 0.755）之间存在统计学显著相关性（P < 0.01）。两组咪达唑仑的催眠作用相似。然而，在药代动力学的基础上，建议对晚期肝硬化患者减少咪达唑仑的剂量。
To study the effects of cirrhosis of the liver on the pharmacokinetics of midazolam single IV (7.5 mg as base) and p.p (15.0 mg as base) doses of midazolam were administered to seven patients with cirrhosis of the liver and to seven healthy control subjects. One cirrhotic patient did not receive the oral dose. The distribution of midazolam in both study groups was alike as indicated by similar values of t1/2.alpha., V1 and Vss. Also the plasma protein binding of midazolam was unchanged in the patients with cirrhosis. The elmination of midazolam was significantly retarded in the patients as indicated by its lower total clearance (3.34 vs. 5.63 ml/min/kg), lower total elmination rate constant (0.400 vs. 0.721 h-1), and longer elimination half-life (7.36 vs 3.80 h). The bioavailability of oral midazolam was significantly (P < 0.05) higher in patients than controls (76% vs. 38%). The antipyrine-half-life was 32.4 h in the patients and 11.8 h in the controls. There were statistically significant (P < 0.01) correlations between the clearances of the two drugs (r = 0.680) and between their half-lives (r = 0.755). The hypnotic effects of midazolam were similar in both groups. However, on a pharmacokinetic basis of reduced dosage of midazolam to patients with advanced cirrhosis of the liver is recommended.