PII-56The assessment of regional drug absorption of free acid and sodium salt formulations of KS01017 as compared to conventional oral administration in healthy volunteers

Abstract

BACKGROUND/AIM KS01017 is a drug being developed for the treatment of dyslipidemia. The aim of the study was to determine the relative bioavailability of KS01017 in free acid and sodium salt form following administration in the distal small bowel (DSB) and colon as compared to conventional oral administration. METHODS In a 3-way crossover study, 12 healthy subjects were divided into 2 groups and administered 250 mg KS01017, with group 1 receiving the free acid treatments and group 2 receiving the sodium salt treatments. Delivery to the DSB and colon was by the use of the Enterion© capsule that releases drug upon activation. Serial blood samples were drawn and pharmacokinetic parameters were obtained from the plasma data. RESULTS The peak (Cmax) and total (AUCinf) exposure values of KS01017 following the various treatments are given in the following table. Mean (%CV) PK parameters for KS01017 Treatment Cmax (ng/mL) AUCinf (ng*hr/mL) Free acid Capsule 3506 (50) 12884 (24) Na Salt Capsule 4677 (34) 14101 (13) Free acid DSB 1033 (38) 3943 (78) Na Salt Colon 2308 (71) 7345 (68) Free acid Colon 496 (92) 1663 (83) Na Salt Colon 428 (76) 1799 (83) The AUCinf values indicate that the sodium salt showed a higher extent of absorption as compared to the free acid form. The difference between the salt and acid was highest for the DSB and lowest for colonic administration. Relative bioavailability for DSB administration was lower for both the salt form (52%) and acid form (30%) as compared to the oral gelatin capsule. Relative bioavailability for colonic administration was only 13% for the salt and free acid form as compared to the oral gelatin capsule. CONCLUSIONS The relative bioavailability of KS01017 was highest after oral gelatin capsule administration, followed by administration to the DSB and colon. Clinical Pharmacology & Therapeutics (2005) 79, P51–P51; doi: 10.1016/j.clpt.2005.12.181