TABLE VIII.

Sex differences in hepatic clearance by route of metabolism/elimination

Phase I enzymes
METABOLIC ROUTE	Model Substrates	Drugs metabolized by route	Sex-Specific Activty
CYP1A	Caffeine, nicotine paracetamol (acetaminophen)	Clomipramine, clozapine, olanzapine, paracetamol, tacrine, theophylline	M>F
CYP2C9	Dapsone, (S)-mephenytoin	Ibuprofen, (S)-warfarin, tolbutamide, fluvastatin, glipizide, losartan, irbesartan, piroxicam, tolbutamide, phenytoin, fluvastatin, nelfinavir	M=F
CYP2C19	(S)-Mephenytoin Diazepam	Lansoprazole, omeprazole, hexobarbital, mephobarbital, citalopram, celecoxib, irbesartan, imipramine, piroxicam, propranolol (in part)	M=F
CYP2D6	Dextromethorpha ndebrisoquine, sparteine	Codeine, encainide, flecainide, fluoxetine, hydrocodone, metoprolol, paroxetine, mexilitine, phenformin, propranolol, sertraline, timolol, haloperidol, clomipramine, desipramine, imipramine, propafenone, testosterone	M<F
CYP2E1	Chlorzoxazone	--	M>F
CYP3A	Midazolam, dapsone, cortisol, lidocaine, nifedipine, erythromycin, cortisol	Alprazolam, alfentanil, astemizole, atorvastatin, carbamazepine, cisapride, clarithromycin, cyclosporin, cyclophosphamide, diazepam, diltiazem, erythromycin, estradiol, fentanyl, indinavir, itraconazole, ketoconazole, lovastatin, quinidine, nimodipine, nisoldipine, quinidine, ritonavir, verapamil, tacrolimus, simvastatin, vincristine, vinblastine, tamoxifen, tirilazad, troglitazone	M=F; F>M
Phase II enzymes
METABOLIC ROUTE	Model Substrates	Drugs metabolized by route	Sex-Specific Activty
UDP- glucuronosyl- transferases	Caffeine	Clofibric acid, diflusinal, ibuprofen, mycophenolate mofetil, paracetamol, zidovudine	M>F
Sulfo- transferases	Caffeine	--	M>F
N-Acetyl- transferases	Caffeine, dapsone	Catecholamine derivatives, mercaptopurine, isoniazid, hydralazine	M=F
Methyl- transferases	Norepinephrine, epinephrine	Ercaptopurine, azathioprine, dopamine, levodopa, 6-mercaptopurine, 6- thioguanine, tazathioprine	M>F