Mixed pharmacokinetic population study and diffusion model to describe ciprofloxacin lung concentrations

The pharmacokinetics of ciprofloxacin in plasma and lung tissue at steady-s tate (500 mg b.i.d.) were studied in 38 patients subjected to lung surgery for bronchial epithelioma. The mean characteristics of the patient populati on were: age = 60 years (range: 48-70), weight = 70 kg (47-95), height = 16 5 cm (range 160-170) and serum creatinine = 85 muM (range 62-168). Plasma s amples, two for each patient and lung samples, one for each patient, were o btained and analyzed. Seven groups were made according to the time of sampl ing after ingestion of the 5th dose. A three-compartment model was used to describe ciprofloxacin kinetics in plasma and lung. The non-linear mixed ef fect model approach was used to estimate the mean and variance of the pharm acokinetic parameters. The mean +/- SD of the estimates (coefficient of var iation of interindividual variability as a percentage) were central volume of distribution, 39.45 +/- 52.47 1 (133%); steady-state volume of distribut ion, 145.86 +/- 97.51 1 (60%), clearance of influx into lung tissue, 35.83 +/- 22.57 l/h (63%), extrapolated elimination rate constant, 0.173 +/- 0.25 /h and extrapolated elimination half-life, 4.02 +/- 0.89 h. The mean +/- SD ciprofloxacin concentration versus time curve in plasma and lung at steady state was simulated using pharmacokinetic parameters and lung physiologica l parameters, another approach was studied to model the transport of ciprof loxacin into the lung tissue by diffusion. Ciprofloxacin concentration-time history was obtained both by experiments or simulations. The ciprofloxacin level in the lung tissue followed the ciprofloxacin plasma level with a la g time resulting from the time necessary for ciprofloxacin to diffuse throu gh the lung. (C) 2001 Elsevier Science Ltd. All rights reserved.