Renal differential ageing process and ofloxacin pharmacokinetics in the elderly

Ageing generates an important inter- and intra-individual variability in dr ug pharmacokinetics. The increasing frequency of ofloxacin adverse effects in elderly patients results from increased ofloxacin plasma levels about tw o or threefold over normal concentrations. A retrospective study of ofloxac in population pharmacokinetics in 17 elderly patients (83.6 +/- 6.8 years) shows the existence of three subgroups according to ofloxacin total clearan ce [group 1: 1.14 1/h, group 2: 4.37 1/h and group 3: 15.08 1/h] reflecting the important inter-individual variability. No correlation between this cl earance and creatinine clearance, nor between this clearance and age, could be established, showing the limits of traditional drug monitoring in the e lderly. Ofloxacin pharmacokinetic parameters estimated by the non-parametri c software NPEM2 in the 17 elderly patients (absorption rate constant, K-a: 2.655 +/- 1.256 h(-1); apparent volume of distribution related to weight, Vs: 1.272 +/- 0.778 1/kg; elimination rate constant, Ei: 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, an d also the interest of adaptive control of a drug regimen.