Pharmacokinetics of ketoprofen enantiomers after intravenous administration of racemate in camels: effect of gender

The pharmacokinetics of ketoprofen (KP) enantiomers were studied in ten fem ale and eight male camels after a single intravenous dose (2.0 mg/kg) of ra cemic KP. A high performance liquid chromatographic (HPLC) method was devel oped for the quantitation of the R- and S-enantiomers without derivatizatio n of the samples using a S,S-Whelk-01 chiral stationary phase column. The d ata collected (median and range) were as follows: the areas under the curve to infinity (AUC) (mug/mL per h) were 22.4 (13.5-29.7) and 19.8 (13.8-22.1 ) for R- and S-KP, respectively, in female camels while the corresponding v alues in male camels were 16.0 (12.9-22.4) and 14.4 (11.0-19.3). In both se xes, the AUC for the R-enantiomer was significantly larger than that of the S-enantiomer. Total body clearances (CI,) were 44.6 (33.7-74.1) and 50.6 ( 45.2-72.4) mL/kg per h for R- and S-KP, respectively, in female camels and were 62.8 (44.6-77.8) and 69.6 (51.8-91.1) mL/kg per h for R- and S-KP, res pectively, in male camels. In both sexes of camels, the Cl-t values for R-K P were significantly lower than its corresponding antipode. The steady-stat e volumes of distribution (V-ss) were 97.9 (82.8-147.2) and 102.0 (90.1-169 .0) mL/kg for R- and S-KP, respectively, in female camels and were signific antly different from each other, while the respective values in male camels were 151.5 (105.3-222.3) and 154.0 (114.7-229.0) mL/kg but were not signif icantly different from each other. The volumes of distribution (area) follo wed a similar pattern, where the values for R- and S-KP in female camels we re 118.5 (95.6-195.2) and 137.6 (115.8-236.2) mL/kg, respectively, and the respective values in male camels were 215.6 (119.1-270.1) and 229.1 (143.3- 277.4) mL/kg. The elimination half-lives (t(1/2 beta)) were 1.88 (1.42-2.34) h and 1.83 ( 1.67-2.26) h for R- and S-KP, respectively, in female camels and were signi ficantly different from each other, while the corresponding values in male camels were 2.11 (1.50-4.20) and 2.33 (1.52-3.83) h for R and S-K, respecti vely, but were not significantly different from each other. The mean reside nce time followed a similar pattern. All pharmacokinetic parameters for R- and S-K in female camels were significantly different from their correspond ing values in male camels. The extent of protein binding for R- and S-KP wa s evaluated in vitro by ultrafiltration. The extents of protein binding for R- and S-KP were not significantly diffe rent from each other when each enantiomer was supplemented separately. Howe ver, when the enantiomers were supplemented together, protein binding of R- KP was significantly higher than that of S-KP in female but not in male cam els.