Effect of dose on serum pharmacokinetics of intravenous ciprofloxacin with identification and characterization of extravascular compartments using noncompartmental and compartmental pharmacokinetic models

Abstract

The effect of dose on the pharmacokinetics of ciprofloxacin in serum and urine following single intravenous doses of 100, 150, and 200 mg was studied in nine healthy volunteers. Mean peak levels in serum were 1.4, 2.0, and 3.2 mg/liter for the 100-, 150-, and 200-mg doses, respectively. The data on concentrations in serum were best described by a three-compartment pharmacokinetic model. The terminal half-life (from noncompartmental analysis) averaged between 4.2 and 4.6 h. Average urinary recovery ranged between 45.8 and 48.1%. The average renal clearance of ciprofloxacin was 2.9- to 3.4-fold greater than the measured creatinine clearance. Total serum and renal clearances decreased with increasing dose; however, this was not statistically significant (P greater than 0.05; repeated-measures analysis of variance). Ciprofloxacin was well tolerated by all subjects. In this dose range, ciprofloxacin pharmacokinetics are independent of dose.