Pharmacokinetics of ciprofloxacin in cystic fibrosis

Abstract

We studied the pharmacokinetics of ciprofloxacin in 12 adult males with and 12 adult males without cystic fibrosis (CF). In a randonized crossover sequence, the subjects received 200 mg intravenously or 750 mg orally. With intravenous dosing, subjects also received 651 mg of iothalamate, a marker of glomerular ifitration, and 700 mg of antipyrine, an indicator of hepatic oxidative drug metabolism. Pharmacokinetic parameters were determined by model independent methods. In the CF subjects, the ciprofloxacin concentration in serum during the first hour after intravenous administration was higher, and the oral absorption rate was slower. Other parameters did not differ between the groups. Mean concentrations in serum 5 min postinfusion were 3.08 and 2.14 ,Ig/mn, and mean peak concentrations after oral dosing were 3.24 and 3.34 ,ug/ml in subjects with and without CF, respectively, Mean values for elimination half-life in all subjects were 4.8 and 5.0 h after intravenous and oral administration, respectively. The mean renal clearances in all subjects after intravenous and oral administration were 19.4 and 14.5 liters/h and accounted for 64 and 47% of the total clearance, respectively. These values were significantly greater than renal iothalamate clearance, indicating that tubular secretion contributed to the renal clearance of ciprofloxacin. A total of 69 and 35.4% of the administered ciprofloxacin was recovered from the urine within 48 h after intravenous and oral administration, respectively. The mean bioavailability was 71.2% and did not differ between the groups. We conclude that similar dosing regimens can be used to treat patients with CF and their normal counterparts.Respiratory infections caused by Pseudomonas aeruginosa, Haemophilus influenzae, and Staphylococcus aureus are responsible for much of the morbidity and mortality in patients with cystic fibrosis (CF) (15). Ciprofloxacin is a quinoline antibiotic which posesses activity against these and other organisms (2,9,19, 31).Patients with CF have altered pharmacokinetics of some drugs as compared with their normal counterparts (15). The purpose of this study was to compare the pharmacokinetics of ciprofloxacin after intravenous and oral administration in subjects with CF to that in subjects without any known disease states. MATERIALS AND METHODSSubjects. A total of 12 male subjects with CF (ages 18 to 34) and 12 male volunteers without CF (ages 23 to 32) were enrolled in the study after informed consent was obtained. The study was approved by the Human Subjects Review Board at our university. All subjects abstained from alcohol-containing beverages for 72 h before and 48 h after administration of the study drugs. Subjects with CF abstained from alcohol but took their usual medications (multivitamins, pancreatic enzymes, and bronchodilators). All subjects were reexamined and laboratory tests were repeated within 72 h after the final dose of ciprofloxacin.Drug administration. In a randomized, crossover sequence, volunteers received 200 mg of ciprofloxacin...

Population Pharmacokinetics and Use of Monte Carlo Simulation To Evaluate Currently Recommended Dosing Regimens of Ciprofloxacin in Adult Patients with Cystic Fibrosis

“…Interestingly, the pharmacokinetic description of intravenous ciprofloxacin in this study differs from that found in previously published CF studies (2,4,21). For comparison purposes, the pharmacokinetic parameters from those studies, in addition to a study looking at acutely ill, non-CF patients, are summarized in Table 3.…”

“…Our subjects exhibited a lower clearance and volume of distribution than did those in other studies. The CL T is roughly half, in comparison to the clearances obtained from CF patients in other studies (2,4,21). Differences between study populations that may account for this apparent discrepancy include age, degree of acute illness, and differences in genotypes.…”

“…There are presently no published studies involving intravenous ciprofloxacin in CF patients in which compartmental pharmacokinetic analysis was performed (2,4,21). We found that a two-compartment model best described the disposition of ciprofloxacin in our adult CF population.…”

“…In addition, ciprofloxacin has consistently demonstrated synergistic activity with other antipseudomonal agents against multiple-drug-resistant P. aeruginosa isolates obtained from CF patients (18). With these attributes, it is not surprising that ciprofloxacin is frequently prescribed for the treatment of pulmonary exacerbations in CF patients.The pharmacokinetics of ciprofloxacin have been extensively evaluated in stable CF patients (4,9,11,14,17,20,23). Results of these studies indicate no significant alterations in pharmacokinetics when patients are compared with normal healthy volunteers.…”

“…The pharmacokinetics of ciprofloxacin have been extensively evaluated in stable CF patients (4,9,11,14,17,20,23). Results of these studies indicate no significant alterations in pharmacokinetics when patients are compared with normal healthy volunteers.…”