McQuinn R L, Pentikäinen P J, Chang S F, Conard G J
3M/Riker Laboratories, Inc., St. Paul, MN 55144.
Clin Pharmacol Ther. 1988 Nov;44(5):566-72. doi: 10.1038/clpt.1988.195.
The pharmacokinetics of flecainide were studied in six patients with cirrhosis of the liver and in six healthy subjects after a single 2 mg/kg intravenous dose. Hepatic biotransformation capability before flecainide dosing was assessed by antipyrine challenge. The mean plasma antipyrine t1/2 for patients (42.2 hours) was longer (p less than 0.01) than that for subjects (11.7 hours). For control subjects, the plasma t1/2 of flecainide (9.5 hours) was shorter (p less than 0.01), plasma clearance (9.1 ml/min/kg) was faster (p less than 0.01), and volume of distribution (7.5 L/kg) was smaller (p less than 0.05) compared with corresponding values in patients. Renal clearance did not differ (p greater than 0.05) between the two groups. The mean ratio of renal clearance to plasma clearance for subjects (0.4) was smaller (p less than 0.05) than that for patients. The slower rate of flecainide elimination from plasma in patients is likely due to reduced hepatic biotransformation. In patients with cirrhosis, plasma levels of flecainide may accumulate to unacceptably high levels with usual dosage regimens.
在6例肝硬化患者和6名健康受试者中，静脉注射单剂量2mg/kg氟卡尼后，研究了其药代动力学。在给予氟卡尼之前，通过安替比林激发试验评估肝脏生物转化能力。患者的平均血浆安替比林t1/2（42.2小时）比受试者（11.7小时）长（p<0.01）。与患者的相应值相比，对照组受试者氟卡尼的血浆t1/2（9.5小时）较短（p<0.01），血浆清除率（9.1ml/min/kg）较快（p<0.01），分布容积（7.5L/kg）较小（p<0.05）。两组之间的肾脏清除率无差异（p>0.05）。受试者肾脏清除率与血浆清除率的平均比值（0.4）低于患者（p<0.05）。患者血浆中氟卡尼消除速率较慢可能是由于肝脏生物转化减少所致。在肝硬化患者中，按照常规给药方案，氟卡尼的血浆水平可能会累积到不可接受的高水平。
