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

Ciprofloxacin is a fluoroquinolone antibiotic effective in the treatment of lower respiratory tract infections (LRTI). The aim of this study was to as sess 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 treat ment of elderly patients with mild to moderate LRTI. The pharmacokinetic st udy was performed on a cohort of 17 elderly inpatients. Blood samples were collected in steady state conditions at appropriate intervals. Ciprofloxaci n serum concentrations were analyzed using an HPLC method and pharmacokinet ic parameters were estimated using the WinNonlin software package. The phar macokinetic data were at least partially different from those obtained by o ther authors in elderly patients (lower C-max after iv administration and h igher CL both after iv and oral administration). C-max after a 1-hour 200-m g infusion were similar to those observed during the 500 mg bid peroral reg imen (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 afte r 500 mg bid oral administration than after 200 mg bid iv administration (A UC(0-tau) 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 c onsidered a valid therapeutic approach from the beginning of therapy For mi ld 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 un der 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 be tter pharmacokinetic exposure than the 200 mg iv bid regimen and a cost-eff ective treatment of LRTI. However, because of the great pharmacokinetic int erindividual variability observed a normalized dosage per kg (3 mg/kg/12h i v and 8 mg/kg/12h os) should be considered, especially for body weight >90 kg and. whenever possible, TDM of AUC(0-tau) or at least of C-max should be performed to individualize therapy in this subpopulation.