Steady-state kinetics of bezafibrate retard in hyperlipidemic geriatric patients

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.