dextromethorphan and efavirenz

Rolapitant is a neurokinin-1 receptor antagonist indicated in combination with other antiemetic agents in adults for the prevention of delayed chemotherapy-induced nausea and vomiting. We evaluated the effects of rolapitant oral on the pharmacokinetics of probe substrates for cytochrome P450 (CYP) 2D6 (dextromethorphan), 2C9 (tolbutamide), 2C19 (omeprazole), 2B6 (efavirenz), and 2C8 (repaglinide) in healthy subjects.. This open-label, multipart, randomized, phase 1 study assessed cohorts of 20-26 healthy subjects administered dextromethorphan, tolbutamide plus omeprazole, efavirenz, or repaglinide with and without single, oral doses of rolapitant. Maximum plasma analyte concentrations (C. Rolapitant significantly increased the systemic exposure of dextromethorphan in terms of C. Inhibition of dextromethorphan by a single oral dose of rolapitant 180 mg is clinically significant and can last at least 7 days. No clinically significant interaction was observed between rolapitant and substrates of CYP2C9, CYP2C19, CYP2B6, or CYP2C8. CYP2D6 substrate drugs with a narrow therapeutic index may require monitoring for adverse reactions if given concomitantly with rolapitant.

Topics: Administration, Oral; Adolescent; Adult; Alkynes; Antiemetics; Benzoxazines; Carbamates; Cyclopropanes; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP2C9; Cytochrome P-450 CYP2D6; Dextromethorphan; Drug Combinations; Drug Interactions; Female; Healthy Volunteers; Humans; Male; Middle Aged; Molecular Probes; Neurokinin-1 Receptor Antagonists; Omeprazole; Piperidines; Spiro Compounds; Tolbutamide; Young Adult