Sex-related differences in the pharmacokinetics of oral ciprofloxacin

The oral pharmacokinetics of ciprofloxacin were studied in healthy volunteers to assess the influence of sex on its disposition. Subjects (8 males, 7 females) received a single oral dose of ciprofloxacin 750 mg, blood and urine samples were collected, and ciprofloxacin concentrations were determined. A two-compartment open-model with two or three absorption phases, each one having a fitted independent lag time, best fit the data using a weighted least squares estimator. Univariate and multivariate regression analyses were performed to determine the influence of renal function, Weight, and subject sex on the oral clearance (CLS/F) and apparent steady-state volume of distribution (V-ss/F) of ciprofloxacin. Females had a median C-max of ciprofloxacin that was 30% greater than males and a significantly smaller median (range) V-ss/F: 81.1 (44.8-111.6) versus 170.9 (140.9-213.4), respectively (p < 0.01). In addition, females had increased exposure to ciprofloxacin, with a slower median (range) CLS/F of 28.3 L/h (24.5-33.4) compared to 44.4 L/h (41.4-53.7) for males (p < 0.01). Regression analyses revealed that subject sex was the only significant predictor of CLS/F (p < 0.001), but both bodyweight (p = 0.04) and subject sex (p < 0.005) were significant predictors of V-ss/F. Fixed oral doses of ciprofloxacin will lead to higher maximum concentration and total drug exposure in females compared to males and do not appear to be solely related to weight-based differences.