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Lack of Unique Ciprofloxacin Pharmacokinetic Characteristics in Patients with Cystic Fibrosis
Author(s) -
Reed Michael D.,
Stern Robert C.,
Myers Carolyn M.,
Yamashita Toyoko S.,
PhD Jeffrey L. Blumer
Publication year - 1988
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1988.tb03202.x
Subject(s) - cystic fibrosis , pharmacokinetics , medicine , ciprofloxacin , pharmacology , antibiotics , microbiology and biotechnology , biology
The single‐dose pharmacokinetics of oral ciprofloxacin 750 mg were evaluated in six subjects with cystic fibrosis (CF subjects) and six age, sex and approximate weight‐matched control subjects (controls). In addition, the effect of concurrently administered oral pancreatic enzyme replacement on the pharmacokinetics of ciprofloxacin was studied in 12 CF subjects. Ciprofloxacin t 1/2 , Vss F , CL F , and CL R in the matched CF subjects averaged 4.5 hours, 2.8 L/kg, 2.73 mL/min/kg and 5.7 mL/min/kg, respectively. Forty‐two percent of the ciprofloxacin dose was excreted in the urine (0–48 hours) as the parent compound. No statistically significant differences in these ciprofloxacin pharmacokinetic parameter estimates were observed between CF and control subjects. In three CF subjects and two controls, the urinary excretion of ciprofloxacin and four of its metabolites were similar. In contrast, CF subjects demonstrated a prolonged t max (2.3 versus 1.3 hours P <.05) though ciprofloxacin C max was similar (4.7 versus 3.8 mg/L, NS). The concurrent administration of oral pancreatic enzyme replacement had no effect on the pharmacokinetics of ciprofloxacin. Apparent ciprofloxacin pharmacokinetic parameters in sputum were similar to those observed in serum. Sputum ciprofloxacin concentrations lagged behind serum concentrations but, on average, exceeded serum concentrations for 20 hours of the 24‐hour sampling period. These sputum ciprofloxacin concentrations exceeded the reported MIC 90 for Pseudomonas aeruginosa for approximately 15 hours. These data suggest an oral ciprofloxacin dose of 750 mg administered q8h to promote accumulation and maintenance of sputum drug concentrations well above pathogen MICs for the majority of a dosing interval in patients with CF.