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

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 23; no. 3; pp. 137 - 143
• Main Authors: Al Katheeri, N. A., Wasfi, I. A., Lambert, M., Saeed, A., Khan, I. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.06.2000
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Area Under Curve; Camelus; Chromatography, High Pressure Liquid; Female; Half-Life; Injections, Intravenous; Ketoprofen - blood; Ketoprofen - metabolism; Ketoprofen - pharmacokinetics; Male; Metabolic Clearance Rate; Protein Binding; Sex Factors; Stereoisomerism
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1046/j.1365-2885.2000.00264.x

The pharmacokinetics of ketoprofen (KP) enantiomers were studied in ten female and eight male camels after a single intravenous dose (2.0 mg/kg) of racemic KP. A high performance liquid chromatographic (HPLC) method was developed for the quantitation of the R‐ and S‐enantiomers without derivatization of the samples using a S,S‐Whelk‐01 chiral stationary phase column. The data collected (median and range) were as follows: the areas under the curve to infinity (AUC) (μg/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 values in male camels were 16.0 (12.9–22.4) and 14.4 (11.0–19.3). In both sexes, the AUC for the R‐enantiomer was significantly larger than that of the S‐enantiomer. Total body clearances (Clt) 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, respectively, in male camels. In both sexes of camels, the Clt values for R‐KP were significantly lower than its corresponding antipode. The steady‐state volumes of distribution (Vss) 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 significantly 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 significantly different from each other. The volumes of distribution (area) followed a similar pattern, where the values for R‐ and S‐KP in female camels were 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 (t1/2β) 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 significantly 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‐KP, respectively, but were not significantly different from each other. The mean residence time followed a similar pattern. All pharmacokinetic parameters for R‐ and S‐KP in female camels were significantly different from their corresponding values in male camels. The extent of protein binding for R‐ and S‐KP was evaluated in vitro by ultrafiltration. The extents of protein binding for R‐ and S‐KP were not significantly different from each other when each enantiomer was supplemented separately. However, 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 camels.