OBJECTIVE: To assess the effect of the UGT inhibitor probenecid on the pharmacokinetics of dalcetrapib, an investigational drug whose pharmacologically active thiol form undergoes glucuronidation (fm UGT ≥ 0.25). MATERIALS AND METHODS: A two-way crossover study in 20 healthy subjects. Subjects received a single 600 mg dose of dalcetrapib with or without probenecid (500 mg 4 times daily for 6 days). RESULTS:AUC∞ and Cmax of dalcetrapib thiol were increased by 14% and 21%, respectively, by co-administration of probenecid. CONCLUSIONS: This case study illustrates the difficulty in predicting clinically relevant drug-drug interactions for UGT substrates based only on the fraction metabolized by glucuronidation.
RCT Entities:
OBJECTIVE: To assess the effect of the UGT inhibitor probenecid on the pharmacokinetics of dalcetrapib, an investigational drug whose pharmacologically active thiol form undergoes glucuronidation (fm UGT ≥ 0.25). MATERIALS AND METHODS: A two-way crossover study in 20 healthy subjects. Subjects received a single 600 mg dose of dalcetrapib with or without probenecid (500 mg 4 times daily for 6 days). RESULTS: AUC∞ and Cmax of dalcetrapib thiol were increased by 14% and 21%, respectively, by co-administration of probenecid. CONCLUSIONS: This case study illustrates the difficulty in predicting clinically relevant drug-drug interactions for UGT substrates based only on the fraction metabolized by glucuronidation.
Authors: Mary Phelan; Judith Anzures-Cabrera; David J Carlile; Lucy Rowell; Olaf Kuhlmann; Gerhard Arold; Richard Robson; Darren Bentley Journal: Clin Pharmacokinet Date: 2013-04 Impact factor: 6.447
Authors: Haseeb Sattar; Sarmad Sheraz Jadoon; Ni Yang; Shihong Li; Mingzhen Xu; Yong Han; Adil Ramzan; Weiyong Li Journal: Saudi J Med Med Sci Date: 2020-08-20