Rapid in vivo dissolution of ketoprofen: implications on the biopharmaceutics classification system.
The aim of this paper was to investigate the in vivo dissolution behavior of ketoprofen, a Class II drug according to the Biopharmaceutics Classification System (BCS), in the upper small intestine of dogs. An intubations method was used, where no blocking balloons were used to prevent luminal drug transport along the GI tract. Our design allowed the drug to be transported freely to more distal parts of the GI tract and also, it was supported by a pharmacokinetic study. Pharmacokinetic parameters of ketoprofen were determined in dogs after administering approximately 0.27 mg kg(-1) (solution) or approximately 1.47 mg kg(-1) (suspension) in oral bolus doses. There were not statistical significant differences in plasma concentrations for both formulations, either in the maximum concentrations C(max) or AUC following oral dose administration. The rapid disappearance of ketoprofen from the intestinal lumen, reflected by low mass recovery in the supernatant and sediment of the collected intestinal fluid samples, in comparison to that recovery of the non-absorbable marker phenol red, suggests that ketoprofen is emptying into the small intestine and is rapidly dissolved and absorbed. In this study, the in vivo results clearly show that the absorption rate of ketoprofen is not dissolution limited; therefore ketoprofen would be essentially equivalent to Class I drugs and could be considered for waiver of bioavailability and bioequivalence testing.
Granero
G E
GE
College of Pharmacy, University of Michigan, Ann Arbor, MI, USA. glagra@mail.fcq.unc.edu.ar
Ramachandran
C
C
Amidon
G L
GL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000493:pharmacokinetics; D001702:Biopharmaceutics; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D007660:Ketoprofen / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D010637:Phenolsulfonphthalein; D012995:Solubility; D013810:Therapeutic Equivalency
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007660:Ketoprofen; D010637:Phenolsulfonphthalein