Clozapine Grapefruit juice

Vandel S, Netillard C, Perault MC, Bel AM. Plasma levels of clozapine and desmethylclozapine are unaffected by concomitant ingestion of grapefruit juice. Eur J Clin Pharmacol 2000 56(4) 347-348. 

Lane HY, Jann MW, Chang YC, et al. Repeated ingestion of grapefruit juice does not alter clozapine s steady-state plasma levels, effectiveness, and tolerability. J Clin Psychiatry 2001 62(10) 812-817. 

Ozdemir V, Kalow W, Okey AB, Lam MS, Albers LJ, Reist C, Fourie J, Posner P, Collins EJ, Roy R. Treatment-resistance to clozapine in association with ultrarapid CYP1A2 activity and the C A polymorphism in intron 1 of the CYP1A2 gene effect of grapefruit juice and low-dose fluvoxamine. J Clin Psychopharmacol 2001 21 603-607. 

Cytochrome P450 3A4 is highly expressed in the human small intestinal mucosa, and is responsible for the metabolism of cyclosporine, midazolam, clozapine and saquinavir during passage across the intestinal mucosa. Indeed, inhibition of presystemic metabolic processes is likely to be a factor in a 34% to 103% increase in the bioavailability of nifedipine observed in individuals consuming grapefruit juice. 

Lane HY, Chiu CC, Kazmi Y, Desai H, Lam YW, Jann MW, Chang WH. Lack of CYP3A4 inhibition by grapefruit juice and ketoconazole upon clozapine administration in vivo. Drug Metabol Drug Interact 2001 18(3— 4) 263—78. 

The future of psychopharmacotherapy may include creative dietary or other pharmacological manipulations of the CYP enzyme system to achieve a positive treatment response. Recently, it was demonstrated that levels of cyclosporine (an expensive immunosuppressive agent) were dramatically increased in patients who were concomitantly administered grapefruit juice (Hollander et al. 1995). In other studies, paroxetine and fluoxetine were used to raise desipramine levels in superextensive me-tabolizers who were nonresponsive to standard doses (Kraus et al. 1996). Also, the authors used fluvoxamine to augment olanzapine and clozapine concentrations when a lack of response was obtained at standard or upper-level doses. Because per-pill costs of many of today s newer-generation psychoactive compounds often prove prohibitive, use of dietary and pharmacological CYP inhibitors could have significant pharmacoeconomic implications. 

A2 Cimetidine, fluoroquinolones, grapefruit juice, macrolides, isoniazid, zileuton Acetaminophen, clozapine, haloperidol, theophylline, tricyclic antidepressants, (R)-warfarin... 

There are isolated cases of apparent interactions between clozapine, and ampicillin, buspirone, caffeine, haloperidol, loperamide, modafinil, nefazodone, nicotinic acid, tryptophan, or vitamin C. Grapefruit juice, influenza vaccine mirtazapine, reboxetine, or venlafaxine do not appear to interact Cocaine levels may increase when taken with clozapine. 

Grapefruit juice did not affect the metabolism of clozapine in two studies in a total of 36 schizophrenic patients. ... 

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