Irreversible CYP3A inhibition accompanied by plasma protein-binding displacement: a comparative analysis in subjects with normal and impaired liver function

• Published in: Clinical pharmacology and therapeutics Vol. 85; no. 3; p. 319
• Main Authors: Orlando, R, De Martin, S, Pegoraro, P, Quintieri, L, Palatini, P
• Format: Journal Article
• Language: English
• Published: United States 01.03.2009
• Subjects: Adult; Aged; Blood Proteins - metabolism; Cross-Over Studies; Cytochrome P-450 CYP3A - metabolism; Cytochrome P-450 CYP3A Inhibitors; Double-Blind Method; Enzyme Inhibitors - metabolism; Enzyme Inhibitors - pharmacology; Erythromycin - metabolism; Erythromycin - pharmacology; Humans; Liver - drug effects; Liver - enzymology; Liver - physiology; Liver Diseases - enzymology; Liver Diseases - physiopathology; Male; Middle Aged; Protein Binding - drug effects; Protein Binding - physiology; Quinine - metabolism; Quinine - pharmacology

In this study, quinine was used as a probe substrate and erythromycin as a prototypical irreversible inhibitor of CYP3A to ascertain whether, like reversible CYP inhibition, the magnitude of irreversible inhibition is also strictly dependent on the status of liver function. The effect of erythromyci...