Wills R J, Belshe R, Tomlinsin D, De Grazia F, Lin A, Wells S, Milazzo J, Berry C
Hoffmann-La Roche Inc., Nutley, NJ 07110.
Clin Pharmacol Ther. 1987 Oct;42(4):449-54. doi: 10.1038/clpt.1987.176.
Six patients with chronic liver disease and six sex-, age (+/- 5 years)-, and weight (+/- 5 kg)-matched healthy control subjects received a single dose of two 100 mg tablets rimantadine HCl. Eight additional patients with chronic liver disease who were not matched to healthy subjects received a single dose of two 100 mg tablets of rimantadine HCl. Blood and urine samples were collected and rimantadine concentrations were determined by a GCMS method. The values for maximum plasma concentration, AUC, elimination half-life, and renal clearance were not significantly different between patients and control subjects, independent of the statistical analyses (parametric and nonparametric) used. The mean apparent elimination half-life, volume of distribution, and total clearance in the matched patients with liver disease were 32 hours, 24 L/kg, and 676 ml/min, respectively. Renal clearance and the amount excreted in the urine unchanged were 63 ml/min and 10%, respectively. In conclusion, rimantadine pharmacokinetics were not appreciably altered in patients with less severe chronic liver disease.
6例慢性肝病患者以及6例在性别、年龄(±5岁)和体重(±5千克)方面相匹配的健康对照受试者接受了单剂量的两片100毫克盐酸金刚烷胺片剂。另外8例未与健康受试者匹配的慢性肝病患者接受了单剂量的两片100毫克盐酸金刚烷胺片剂。采集血样和尿样,采用气相色谱-质谱联用(GCMS)方法测定金刚烷胺浓度。无论采用何种统计分析方法(参数法和非参数法),患者与对照受试者之间的最大血浆浓度、曲线下面积(AUC)、消除半衰期和肾清除率的值均无显著差异。在匹配的肝病患者中,平均表观消除半衰期、分布容积和总清除率分别为32小时、24升/千克和676毫升/分钟。肾清除率和尿中未变化药物的排泄量分别为63毫升/分钟和10%。总之,在病情较轻的慢性肝病患者中,金刚烷胺的药代动力学没有明显改变。