Lee J T, Yee Y G, Dorian P, Kates R E
Cardiology Division, Stanford University Medical Center, California 94305.
J Clin Pharmacol. 1987 May-Jun;27(5):384-9. doi: 10.1002/j.1552-4604.1987.tb03035.x.
Hepatic metabolism is the primary process of elimination of propafenone. It therefore is important to understand the effect of altered liver function on the disposition and elimination kinetics of this drug. Patients with abnormal liver function probably will require treatment with propafenone for cardiac arrhythmias; an understanding of the relationship between liver function and the pharmacokinetics of propafenone will provide a rational basis for optimal dosage adjustments in these individuals. Our results demonstrate that both systemic clearance and bioavailability of propafenone are sensitive to variability in liver function. The bioavailability of propafenone is inversely related to the clearance of indocyanine green (ICG), whereas a direct relationship exists between systemic clearance of propafenone and ICG clearance. Comparisons of clinical parameters with the propafenone data yielded interesting results. An overall clinical grading of severity of liver disease based on the presence or absence of portal hypertension (i.e., varices and/or splenomegaly), prior encephalopathy, and ascites did not correlate well with propafenone results. However, albumin, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT) concentrations and prothrombin time values correlated strongly with the overall results. No definite relationships with subjects' age; weight; and hemoglobin, alkaline phosphatase, lactic acid dehydrogenose, cholesterol, blood urea nitrogen, or creatinine levels were detected. These results demonstrate that moderate to severe liver disease significantly affects the absorption and disposition of propafenone. In patients with cirrhosis, and presumably other forms of hepatic dysfunction, careful adjustments of propafenone doses are needed to optimize therapy.
肝脏代谢是普罗帕酮消除的主要过程。因此，了解肝功能改变对该药物处置和消除动力学的影响非常重要。肝功能异常的患者可能需要使用普罗帕酮治疗心律失常；了解肝功能与普罗帕酮药代动力学之间的关系将为这些患者的最佳剂量调整提供合理依据。我们的结果表明，普罗帕酮的全身清除率和生物利用度对肝功能变化均敏感。普罗帕酮的生物利用度与吲哚菁绿（ICG）清除率呈负相关，而普罗帕酮的全身清除率与ICG清除率呈正相关。将临床参数与普罗帕酮数据进行比较得出了有趣的结果。基于是否存在门静脉高压（即静脉曲张和/或脾肿大）、既往肝性脑病和腹水对肝病严重程度进行的总体临床分级与普罗帕酮的结果相关性不佳。然而，白蛋白、总胆红素、血清谷氨酸草酰乙酸转氨酶（SGOT）浓度和凝血酶原时间值与总体结果密切相关。未检测到与受试者年龄、体重以及血红蛋白、碱性磷酸酶、乳酸脱氢酶、胆固醇、血尿素氮或肌酐水平有明确关系。这些结果表明，中度至重度肝病会显著影响普罗帕酮的吸收和处置。对于肝硬化患者以及可能患有其他形式肝功能障碍的患者，需要仔细调整普罗帕酮剂量以优化治疗。
