Ciprofloxacin disposition in elderly patients with LRTI being treated with sequential therapy (200 mg intravenously twice daily followed by 500 mg per os twice daily): Comparative pharmacokinetics and the role of therapeutic drug monitoring

Ciprofloxacin is a fluoroquinolone antibiotic effective in the treatment of lower respiratory tract infections (LRTI). The aim of this study was to assess the pharmacokinetic appropriateness of a standard switch iv/os regimen of ciprofloxacin (200 mg iv bid for 3 to 5 days followed by 500 mg os bid for 7 to 10 days) frequently used in routine clinical practice in the treatment of elderly patients with mild to moderate LRTI. The pharmacokinetic study was performed on a cohort of 17 elderly inpatients. Blood samples were collected in steady state conditions at appropriate intervals. Ciprofloxacin serum concentrations were analyzed using an HPLC method and pharmacokinetic parameters were estimated using the WinNonlin software package. The pharmacokinetic data were at least partially different from those obtained by other authors in elderly patients (lower C(max) after iv administration and higher CL both after iv and oral administration). C(max) after a 1-hour 200-mg infusion were similar to those observed during the 500 mg bid peroral regimen (2.1 ± 0.9 mg/L vs 2.6 ± 1.0 mg/L; p = 0.054). The absolute oral bioavailability (84.1%) allowed a total body exposure 2.1-fold greater after 500 mg bid oral administration than after 200 mg bid iv administration (AUC(0-τ) 11.4 ± 4.3 mg/L · h vs 5.5 ± 1.8 mg/L · h). The results show that in malabsorption-free elderly patients a regimen of 500 mg os bid may be considered a valid therapeutic approach from the beginning of therapy for mild to moderate LRTI caused by sensitive microrganisms (MIC < 0.1 mg/L). In fact, because the peak serum level to MIC ratio (C(max)/MIC) and the area under the inhibitory serum concentration-time curve (AUIC 24 = AUC(24h)/MIC) are actually considered major pharmacodynamic determinants for the outcome of treatment with fluoroquinolones, this regimen could guarantee both a better pharmacokinetic exposure than the 200 mg iv bid regimen and a cost-effective treatment of LRTI. However, because of the great pharmacokinetic interindividual variability observed a normalized dosage per kg (3 mg/kg/12h iv and 8 mg/kg/12h os) should be considered, especially for body weight > 90 kg and, whenever possible, TDM of AUC(0-τ) or at least of C(max) should be performed to individualize therapy in this subpopulation.