|
CYP isoenzymes
# = found in lung tissue | |||||||
| CYP3 1 subfamily, 3 genes, 2 pseudogenes
(drug metabolism) 3A3 is an artefact. | |||||||
| Isoenzyme | Substrates | Inducer | Inhibitor | Alleles | Effects (alleles, interactions) | ||
| CYP3A4# (about 30% of liver CYP, 70% of small intestinal CYP) |
terfenadine, astemizole, azelastine,
(fexofenadine is safe),
midazolam, alprazolam, triazolam,
cyclosporin A, tacrolimus,
haloperidol,
tirilazad,
Ca channel blockers (diltiazem, verapamil,
felodopine, ..),
cisapride,
pimozide, alfentanil, sufentanil, fentanyl, | rifampicin, rifabutin,
glucocorticoids, carbamazepine, phenobarbitone,
phenytoin, artemisinin, ? nevirapine
In addition some xenobiotics stimulate CYP3A4 mediated degradation of other substrates ("positive cooperativity"), or even themselves. [flavonoids and some steroids] |
clotrimazole, ketoconazole, itraconazole > fluconazole,
miconazole;
SSRIs (sertraline, fluoxetine, ..), propofol, vinblastine, vincristine, ergotamine, progesterone, dexamethasone, bromocriptine, cimetidine { >>> ranitidine }, quinidine; irreversible inhibition occurs with some 17-alpha ethinyl substituted steroids (ethinyl-estradiol, ?mifepristone), and grapefruit juice! | *1 .. *3 | Marked inter-individual variation in activity;
fatal arrhythmias from pimozide + clarithromycin; astemizole removed from market d/t interactions; A vast number of potential interactions. | ||
| CYP3A5# (and 3A5P1, 3A5P2)
(kidney; small, variable amounts in liver, GIT ) |
midazolam,
caffeine, diltiazem
(cyclosporin)
NOT quinidine or erythromycin | dexamethasone | troleandomycin | *1, *2 | About 1/3 of individuals have significant liver 3A5! | ||
| CYP3A7 | (steroid metabolism)
The major fetal liver cytochrome | ||||||
| Last update 2000-1-22 | Author jo@anaesthetist.com |