Perturbation of plasma protein binding is the primary mechanism causing most clinically significant drug interactions with warfarin.
True or False?
Co-administration of bosentan and glyburide results in ~40% lower glyburide exposure and ~30% lower bosentan exposure.
What is a possible mechanism for this interaction?
A. Inhibition of CYP3A or other CYP450 enzyme
B. Induction of CYP3A or other CYP450 enzyme
C. Inhibition of gut transporter BCRP
D. Reduced solubility of both agents in the gut
E. A pharmacodynamic interaction
Co-administration of glyburide and bosentan results in an increased risk of liver enzyme elevations.1 This is likely a result of the pharmacokinetic interaction described in Question 2.
True or False?
Consider a new drug being developed for the treatment of a common indication, such as diabetes mellitus or high blood pressure. In vitro and preclinical studies indicate the compound is extensively metabolized, primarily by CYP3A and partially by CYP2C19. The compound does not appear to be an inducer or inhibitor of any CYP450 enzymes, but it is a potential inhibitor of P-glycoprotein (P-gp).
What drug interaction studies should the company developing the compound consider?
A. A DDI study with digoxin
B. Two DDI studies – one with midazolam and one with itraconazole
C. Two DDI studies – one with itraconazole and one with fluconazole
D. All of the above
E. A and C
Presented by the PhRMA Foundation Safe and Effective Prescribing Project
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