piperidines and Hyperparathyroidism--Secondary

Evocalcet is a novel calcimimetic agent for the treatment of secondary hyperparathyroidism (SHPT). This study evaluated the effects of evocalcet on inhibition and induction of cytochrome P450 (CYP) isozymes. Although drug interactions arising from reversible inhibition of CYP isozymes by evocalcet were considered unlikely based on the results of in vitro studies and static model analyses, the potential for evocalcet to cause time-dependent inhibition of CYP3A or induction of several CYP isozymes could not be ruled out. Therefore, a clinical drug-drug interaction (DDI) study to evaluate the effects of evocalcet on the pharmacokinetics (PKs) of probe substrates for CYP isozymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP3A) was conducted in healthy male volunteers using a novel cocktail combination. Evocalcet did not significantly affect the PKs of the probe substrates, confirming that CYP-mediated interactions were unlikely.

Topics: Administration, Oral; Adult; Alkynes; Benzoxazines; Calcimimetic Agents; Carbamates; Cells, Cultured; Cyclopropanes; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Healthy Volunteers; Hepatocytes; Humans; Hyperparathyroidism, Secondary; Inhibitory Concentration 50; Isoenzymes; Male; Naphthalenes; Oxidation-Reduction; Piperidines; Primary Cell Culture; Pyrrolidines; Theophylline; Young Adult