Inhibition of cytochrome P450 3A: relevant drug interactions in gastroenterology.
Cytochrome P450 3A (CYP3A) is involved in biotransformation of more than half of all drugs currently available. Drug interactions by inhibition of CYP3A are of major interest in patients receiving combinations of drugs. Some interactions with CYP3A inhibitors also involve inhibition of the multidrug export pump, P-glycoprotein. An increasing number of adverse drug reactions might be avoided on the basis of knowledge about CYP3A substrates and inhibitors. This article summarizes some examples of such interactions relevant to gastroenterologists. Serious cases by coadministration of CYP3A inhibitors resulting in acute hepatitis, hypotension, rhabdomyolyis, torsade de pointes, sedation, or ergotism are presented: interactions with azole antifungals (ketoconazole, itraconazole, fluconazole), HIV protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir), macrolide antibiotics (clarithromycin, erythromycin), and grapefruit juice. In addition, 1 case is reported who presented the highest trough levels of the CYP3A substrate budesonide in serum ever measured. Practitioners have to be aware of the high potential of metabolic drug interactions when they prescribe a CYP3A inhibitor. It is wise to check carefully comedication in patients complaining of side effects with substrates of CYP3A.
Sagir
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A
Klinik für Gastroenterologie, Hepatologie und Infektiologie des Universitätsklinikums Düsseldorf, Deutschland.
Schmitt
M
M
Dilger
K
K
Häussinger
D
D
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000935:Antifungal Agents / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000502:physiology; D001628:Beverages; D019819:Budesonide / Q000494:pharmacology / Q000627:therapeutic use; D032083:Citrus paradisi; D051544:Cytochrome P-450 CYP3A; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors* / Q000502:physiology
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents; D017320:HIV Protease Inhibitors; D019819:Budesonide; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating