Population pharmacokinetics of rufloxacin in patients with acute exacerbations of chronic bronchitis

The pharmacokinetics of rufloxacin were evaluated in patients with acute exacerbations of chronic bronchitis. The drug was administered once-a-day for 10 consecutive days following two different dosage schedules. The first group of 56 patients was given a loading dose of 300 mg on day 1 and 150 mg on the subsequent 9 days. A second group of 55 patients received a loading dose of 400 mg followed by 200 mg for the subsequent 9 days. In each patient, three blood samples were collected during and after treatment. Rufloxacin plasma levels were determined by high performance liquid chromatography. A one-compartment model for repeated doses was employed to estimate the pharmacokinetic parameters. The data were analysed by nonlinear mixed effects modelling using the NONMEM program. The apparent clearance and volume of distribution were found to depend on body weight and gender: the elimination half-life in males (mean weight 73.7 kg) being 30 h and in females (mean weight 71.7 kg) 27 h (68% prediction intervals 9.5–93.9 and 8.6–85.4 h, respectively). The calculated peak plasma concentration at steady state for the 200 mg per day regimen was 4.81 mg/l, while the trough concentration was 2.75 mg/l. The pharmacokinetic parameters of rufloxacin were close to those measured in previous formal studies in a small number of patients but with numerous blood samples. The study also showed that a 200 mg daily oral dose of rufloxacin preceded by a loading dose of 400 mg produced steady state plasma concentrations above the minimum inhibitory concentrations for most susceptible pathogens.