PHAR 430 Lecture Notes - Lecture 6: Cytochrome P450, Grapefruit Juice, Saquinavir
Document Summary
Categories of cyp inhibitors: reversible inhibition, quasi-irreversible inhibition. Increased incidence of side effects of one or more co-administered drugs, and possible of the inhibiting drug. Ritonavir = substrate, inhibitor and inducer of cyp3a4. Ritonavir inhibits metabolism of hiv protease inhibitors = boosted affect of saquinavir. Azole antifungals = cyp3a4 reversible inhibitors; macrolides = cyp3a4 quasi-irreversible inhibitors. The antifungals/abx reduce metabolism of the immunosuppressants = more immunosuppressant effect. This is also more cost effective b/c the immunosuppressants are really expensive. Anastrozole, vorozole, letrozole = reversible inhibitors of cyp19 (aromatase, a steroidogenic cyp enzyme that converts androgens to estrogen) Prevents estrogen formation for breast cancer treatment. Grapefruit juice contains 2 compounds that inhibit intestinal. Cyp3a4/p-gp decreases 1st pass metabolism of these drugs. Blood levels of drugs can rise by 50-100% over normal. Note: not all drugs that can produce enzyme inhibition of cyp enzymes cause drug-drug interactions in vivo. Most likely due to the very low doses used in patients.
