Biopharmaceutical evaluation of ketoprofen following intravenous, oral, and rectal administration in dogs.
The influence of the hydrophilicity of three suppository bases on the rectal absorption of ketoprofen was studied. Absorption characteristics of ketoprofen were compared after intravenous, oral, and rectal administrations of 100 mg of drug given in a crossover design to five dogs. Rectal formulations included an aqueous solution and three suppository formulations. After oral dosing, ketoprofen was rapidly absorbed (time of maximum concentration, tmax: 0.83 +/- 0.61 h), and a comparison with the intravenous solution indicated a complete bioavailability of 0.90 +/- 0.10. After rectal administration, the rate of absorption, as evaluated with tmax and mean absorption time, was always slower than after oral dosing. A high variability was observed in the plasma concentrations obtained with suppository formulations; bioavailability values were approximately 20% lower than those from the oral solutions. No statistical difference in bioavailability and peak concentrations between the three suppository formulations was observed. Time of peak concentrations, mean absorption times, and fractions of the dose absorbed 6 h post administration did not show a difference in rate of ketoprofen absorption from the three suppository formulations. This study did not reveal a relationship between rate and extent of ketoprofen rectal absorption and the hydrophilicity of the suppository bases tested.
Department of Clinical Pharmacology, F. Hoffmann-La Roche, Ltd., Basel, Switzerland.
M
M
Schmitt
T W
TW
Guentert
D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D007275:Injections, Intravenous; D007660:Ketoprofen / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D013056:Spectrophotometry, Ultraviolet
D007660:Ketoprofen