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 (CL(S)/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) CL(S)/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 CL(S)/F (p < 0.001), but both body weight (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.
Overholser
Brian R
BR
Purdue University School of Pharmacy and Pharmacal Sciences, Department of Pharmacy Practice, W7555 Myers Building, WHS, 1001 West 10th Street, Indianapolis, IN 46202, USA.
Kays
Michael B
MB
Forrest
Alan
A
Sowinski
Kevin M
KM
D000328:Adult; D000465:Algorithms; D000890:Anti-Infective Agents / Q000493:pharmacokinetics* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000493:pharmacokinetics* / Q000652:urine; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008954:Models, Biological; D012727:Sex Characteristics; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
D000890:Anti-Infective Agents; D002939:Ciprofloxacin