Epelsiban Besilate

Open‐label single‐ and double‐blind repeat‐dose studies in healthy female volunteers were conducted to investigate the pharmacokinetics (PK) and safety/tolerability of epelsiban total daily doses ranging from 600 to 900 mg. In 1 study (n = 12), epelsiban was dosed at 300 or 450 mg twice daily (every 12 hours) for a single day. In the repeat‐dose double‐blind study, epelsiban and placebo were administered to 31 subjects as 200 mg 3 times daily, 300 mg 3 times daily (TID), or 450 mg twice daily (BID) for 14 days. After both single and 14 daily repeat doses, the PK profiles for epelsiban and its metabolite, GSK2395448, remained linear at all administered doses. The exposures at a given total daily dose were also similar between BID and TID dosing regimens. Exposure (AUC0–τ), based on dosing intervals, for both epelsiban and GSK2395448 was similar. However, compared with morning dosing, Cmax was lower after evening dosing, possibly because of a food effect. The highest accumulation of epelsiban and GSK2395448 exposures (AUC0–τ) was approximately 34% for each after repeat dosing, consistent with the short half‐life. At total daily doses of 600 and 900 mg, epelsiban was generally well tolerated, and there were no significant safety concerns identified.

Camphanic acid chloride has proven to be an efficient chiral derivatization reagent for determination of stereoisomers.

The utility of chemical derivatization of various stereoisomers containing hydroxy functional groups with camphanic acid chloride in the presence or absence of a base is highlighted. This procedure is shown to be relatively simple, fast and a cost-effective method of separating racemic drugs and stereoisomeric metabolites in biological matrices. Camphanic derivatives contain two additional chirogenic centers, which are found to enhance stereoisomeric separation on both traditional and chiral stationary phases.

Four methodologies described herein for separation of multiple stereoisomers in biological samples confirm camphanic acid chloride to be a powerful chiral reagent for stereoisomeric resolution for drug metabolism and PK applications.