Evaluation of the effect of rifampin on the pharmacokinetics of the Smoothened inhibitor glasdegib in healthy volunteers

British Journal of Clinical Pharmacology
M Naveed ShaikRobert R Labadie

Abstract

This study aimed to evaluate the effect of a strong CYP3A inducer, rifampin, on glasdegib pharmacokinetics in healthy volunteers. In an open-label, fixed-sequence, two-period Phase 1 study, subjects received a single 100-mg oral dose of glasdegib alone or following once-daily pre-treatment with 600 mg rifampin. Glasdegib pharmacokinetics were calculated using a noncompartmental analysis. Twelve healthy male volunteers (3 whites, 5 blacks and 4 others) were enrolled in the study. Mean age, weight, height and body mass index was 37.8 years, 83.0 kg, 177.3 cm and 26.5 kg (m2 ) -1 , respectively. When dosed alone, glasdegib geometric mean (% coefficient of variation) area under the plasma concentration-time curve from time zero to infinity (AUCinf ) was 8145 ng × h ml-1 (23%) and maximum observed concentration (Cmax ) was 703.2 ng ml-1 (19%). With rifampin, glasdegib AUCinf and Cmax decreased, with an adjusted geometric mean ratio (90% confidence interval) 29.66% (26.17-33.62) for AUCinf and 64.71% (57.21-73.19) for Cmax . Mean terminal half-life decreased from 13.39 to 5.11 hours, geometric mean apparent oral clearance increased from 12.27 to 41.38 l h-1 , whereas median time to Cmax remained similar (1.50 vs. 1.25 hours) in the p...Continue Reading

References

Oct 1, 1975·Clinical Pharmacology and Therapeutics·G R Wilkinson, D G Shand
Sep 17, 2008·Genes & Development·Markku Varjosalo, Jussi Taipale
Feb 9, 2012·ACS Medicinal Chemistry Letters·Michael J MunchhofGeorge T Tkalcevic
Nov 13, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Andrew J WagnerAnthony B El-Khoueiry
Feb 4, 2016·Development·Raymond Teck Ho LeePhilip W Ingham
Nov 22, 2016·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Justine L LamM Naveed Shaik
Oct 22, 2017·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators
Oct 22, 2017·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators

❮ Previous
Next ❯

Citations

Jan 17, 2019·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Richard L Carpenter, Haimanti Ray
Apr 13, 2019·Clinical Pharmacology in Drug Development·Naveed ShaikRobert Roland LaBadie
Aug 23, 2019·Future Oncology·Anna Wolska-Washer, Tadeusz Robak
Feb 7, 2020·Expert Opinion on Pharmacotherapy·Xavier Thomas, Maël Heiblig
Jul 20, 2020·Annals of Hematology·Juan Eduardo Megías-VericatPau Montesinos
Nov 21, 2020·Journal of Oncology Pharmacy Practice : Official Publication of the International Society of Oncology Pharmacy Practitioners·Valerie ReliasIlene Galinsky
May 18, 2021·Expert Review of Clinical Pharmacology·Luke K FostvedtAna Ruiz-Garcia

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.