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Sex‐Related Differences in the Pharmacokinetics of Oral Ciprofloxacin
Author(s) -
Overholser Brian R.,
Kays Michael B.,
Forrest Alan,
Sowinski Kevin M.
Publication year - 2004
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 - 10.1177/0091270004266843
Subject(s) - ciprofloxacin , pharmacokinetics , medicine , urine , renal function , volume of distribution , antibiotics , chemistry , biochemistry
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.