[Renal differential aging processes and ofloxacin pharmacokinetics in the elderly]

Abstract

Ageing generates an important inter- and intra-individual variability in drug pharmacokinetics. The increasing frequency of ofloxacin adverse effects in elderly patients results from increased ofloxacin plasma levels about two or threefold over normal concentrations. A retrospective study of ofloxacin population pharmacokinetics in 17 elderly patients (83.6 +/- 6.8 years) shows the existence of three subgroups according to ofloxacin total clearance [group 1: 1.44 l/h, group 2: 4.37 l/h and group 3: 15.08 l/h] reflecting the important inter-individual variability. No correlation between this clearance and creatinine clearance, nor between this clearance and age, could be established, showing the limits of traditional drug monitoring in the elderly. Ofloxacin pharmacokinetic parameters estimated by the non-parametric software NPEM2 in the 17 elderly patients (absorption rate constant, Ka: 2.668 +/- 1.256 h-1; apparent volume of distribution related to weight, Vs: 1.272 +/- 0.778 l/kg; elimination rate constant, Ks: 0.265 +/- 0.247 10(-3) min/ml/h) are clearly different from those estimated in young adults. These results show the limits of classic drug monitoring in the elderly, and also the interest of adaptive control of a drug regimen.