Neugebauer G, Platt D, Vömel T, Lösch W
Abteilung für Klinische Pharmakologie der Boehringer Mannheim GmbH.
Klin Wochenschr. 1988 Mar 15;66(6):250-6. doi: 10.1007/BF01748166.
The pharmacokinetics of a slow-release formulation of bezafibrate were investigated under steady-state conditions in 19 hyperlipidemic patients between the age of 61 and 87 years and compared to the kinetics in 20 healthy volunteers (age 19-42 years). Maximum serum levels were 1.6-fold higher in the elderly, which was partly due to a diminished renal clearance caused by the reduction in renal function (CLCR 23-81 ml/min) and partly due to a decrease in extrarenal clearance (probably hydroxylation and hydrolysis). Evidence for the additional decrease in extrarenal clearance was provided by the greater decline in total drug clearance than would be anticipated from a mere reduction in glomerular filtration. Thus, dose adjustment of slow-release bezafibrate in elderly patients cannot be based merely on creatinine clearance. In general, it is recommended that bezafibrate retard is substituted by a reduced dose of normal-release bezafibrate below a creatinine clearance of 60 ml/min.
在稳态条件下,对19名年龄在61至87岁之间的高脂血症患者的苯扎贝特缓释制剂的药代动力学进行了研究,并与20名健康志愿者(年龄19 - 42岁)的动力学进行了比较。老年人的血清最高水平高出1.6倍,部分原因是肾功能降低(肌酐清除率CLCR为23 - 81 ml/min)导致肾清除率降低,部分原因是肾外清除率降低(可能是羟基化和水解)。总药物清除率的下降幅度大于仅因肾小球滤过率降低所预期的幅度,这为肾外清除率的额外降低提供了证据。因此,老年患者中苯扎贝特缓释制剂的剂量调整不能仅仅基于肌酐清除率。一般而言,建议在肌酐清除率低于60 ml/min时,用剂量减少的普通释放苯扎贝特替代苯扎贝特缓释制剂。