Gatifloxacin pharmacokinetics in healthy men and women

Purpose To investigate the sex‐based PK of gatifloxacin (GATI) following oral administration. Methods Twelve healthy subjects (6M, 6F) were administered an oral dose of GATI 400 mg. Blood and urine samples were obtained prior to and serially for 48 hours and concentrations were determined by HPLC. PK parameters were estimated by fitting PK models to the concentration‐time data using the MLS estimator in ADAPT II. Cmax and Tmax were determined by visual inspection of the concentration‐time data and secondary PK parameters were determined by standard equations. Univariate linear regression analysis was used to determine the influence of sex, weight and body mass index (BMI), and renal function on the oral clearance (CLs/F) and apparent steady‐state volume of distribution (Vss/F) of GATI. Results Total body weights[mean (SD)] were 83.1(14.9) and 64.1(11.1) kg for men and women, respectively ( p = 0.03). A 1 or 2‐compartment model best‐fit the data, median (range) R 2 = 0.986(0.937–0.998). PK are shown in the Table. Weight‐adjusted Vss/F was 1.58(0.25) and 1.46(0.14) L/kg for males and females, respectively (p= 0.327). Regression analyses revealed that both total body weight (R 2 = 0.63) and BMI (R 2 = 0.68) were predictors of Vss/F. Conclusion Females had a smaller Vss/F than males, at least partly explained by sex‐related differences in weight. Clinical Pharmacology & Therapeutics (2005) 77 , P78–P78; doi: 10.1016/j.clpt.2004.12.190 Data presented as median (range) or mean (SD) if normally distributedCLs/F (L/hr) Vss/F (L) CLr (L/h) Cmax (mg/L) Tmax (h) t 1/2 (h)Men 11.3 (2.1) 128.8 (16.2) 7.5 (1.8) 3.6 (0.8) 0.9 (0.5,1.5) 8.1 (7.0,10.6) Women 9.3 (2.5) 93.5 (21.3) 6.6 (1.6) 4.5 (0.8) 1.1 (0.5,1.5) 7.2 (5.1,16.5)P value * 0.17 <0.01 0.41 0.06 0.52 0.82* based on t‐test or nonparametric equivalent