Understanding the Effect of Hydroxypropyl-β-Cyclodextrin on Fenebrutinib Absorption in an Itraconazole-Fenebrutinib Drug-Drug Interaction Study.

Clinical Pharmacology and Therapeutics
Matthew R DurkPo-Chang Chiang

Abstract

Cyclodextrins are widely used pharmaceutical excipients, particularly for insoluble compounds dosed orally, such as the oral solution of itraconazole, which is frequently used in clinical drug-drug interaction studies to inhibit cytochrome P450 3A. Since cyclodextrins act by forming inclusion complexes with their coformulated drug, they could have an unintended consequence of affecting absorption if they form a strong complex with the potential victim drug in an itraconazole drug-drug interaction study. This observation was made in a drug-drug interaction study with the Bruton's tyrosine kinase (BTK) inhibitor fenebrutinib and itraconazole, in which, relative to the control group, the expected increase in fenebrutinib maximum plasma concentration (Cmax ) was not observed in the itraconazole group, and a delay in time to reach maximum plasma concentration (Tmax ) was observed in the itraconazole group. The in vitro binding constant between fenebrutinib and hydroxypropyl-β-cyclodextrin was determined to be 2 × 105  M-1 , and the apparent permeability of fenebrutinib across a Madin-Darby canine kidney cell monolayer decreased in a cyclodextrin concentration-dependent manner. This observation was confirmed in vivo, in a pentagastri...Continue Reading

References

Aug 4, 1998·Acta Odontologica Scandinavica·W P HolbrookT Loftsson
Feb 19, 2002·Chemical Reviews·Kaneto UekamaTetsumi Irie
Sep 30, 2004·International Journal of Pharmaceutics·Ann Mari SaeternMartin Brandl
Nov 3, 2010·The Journal of Pharmacy and Pharmacology·Thorsteinn Loftsson, Marcus E Brewster
Mar 1, 2011·Regulatory Toxicology and Pharmacology : RTP·Maria Grazia UrsinoFabrizio De Ponti
Feb 16, 2012·Journal of Pharmaceutical Sciences·Thorsteinn Loftsson, Marcus E Brewster
Feb 12, 2013·Current Medicinal Chemistry·C Scarpignato
Jun 6, 2015·Journal of Clinical Pharmacology·Lichuan LiuSarah M Robertson

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Citations

Sep 17, 2021·The AAPS Journal·Ruchika BajajDeanna L Kroetz

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