CYP3A4 effectiveness drugs

Enzyme Induction (CYP3A4) and Drug Design 1119 Tab. 8.4 Clinical toxicities and side-effects of P4503A4 inducers. 

This newest non-BZD hypnotic is a pyrazolopyrimidine derivative with a fuii agonist activity on centrai BZD receptors B2 type. It is an effective hypnotic for the short-term treatment of insomnia. Because of its very short half-life (almost an hour), it may be useful for patients experiencing difficulty falling asleep and in those who wake up at night and who have trouble falling back to sleep. Zaleplon is rapidly absorbed after oral administration and its mean, apparent elimination half-life is similar to that obtained after i.v. infusion. Zaleplon is extensively metabolized in the liver by aldehyde oxidase, and to a lesser extent by CYP3A4. This drug is excreted in the urine (156). 

CIMETIDINE ANTIPSYCHOTICS -CHLORPROMAZINE, CLOZAPINE, HALOPERIDOL, OLANZAPINE, PERPHENAZINE, RISPERIDONE, SERTINDOLE, THIORIDAZINE, ZUCLOPENTHIXOL T plasma concentrations of these antipsychotics, with risk of associated adverse effects - Drugs Acting on the Nervous System, Antipsychotics Cimetidine is an inhibitor of CYP3A4 (sertindole, haloperidol, risperidone) CYP2D6 (chlorpromazine, risperidone, zudopenthixol, thioridazine, perphenazine) and CYP1A2 (clozapine, olanzapine, sertindole, haloperidol) Avoid concomitant use. Choose alternative acid suppression... 

Drug interactions Drugs utilizing the CYP2D6 (i.e., f luoxetine, cimetidine) or the CYP3A4 (i.e, macrolides, antiretrovirals) pathways may inhibit opioid metabolism and potentiate side effects. Drugs such as benzodiazepines and barbiturates should be used cautiously in combination with opioids, as they may potentiate respiratory depression or sedative effects. 

Zhang X, Jones DR, Hall SD (2009) Prediction of the effect of erythromycin, diltiazem, and their metabolites, alone and in combination, on CYP3A4 inhibition. Drug Metab Dispos 37 150-160... 

Lin H-L, Kenaan C, Hollenbeig PF (2012) Identification of the residue in human CYP3A4 that is covalently modified by bergamottin and the reactive intermediate that contributes to the grapefruit juice effect. Drug Metab Dispos 40 998-1006... 

The co-administration of drugs which induce the metabolic enzymes in the liver or small intestine can reduce the plasma concentrations of drugs which are substrates of the enzyme, leading to reduced drug effects. For example, the plasma concentrations of many drugs which are substrates of the enzyme CYP3A4, such as cyclosporine, are decreased by coadministration of rifampicin, which is an inducer of CYP3A4. 

Only a small number of drug interactions have been reported with donepezil. In vitro studies show a low rate of binding of donepezil to cytochrome P-450 (CYP)3A4 or 2D6. Whether or not donepezil has the potential for enzyme induction is not known. No interactions with theophylline, cimeti-dine, warfarin, digoxin, or ketoconazole have been documented. In vitro studies show that inhibitors of CYP3A4 and 2D6 have the potential to inhibit the metabolism of donepezil. The clinical relevance of this is unknown. However, monitoring for possible increased peripheral side effects is advised... 

Buspirone generally is well tolerated and does not cause sedation. Most common side effects include dizziness, nausea, and headaches. Drugs that inhibit CYP3A4 (e.g., verapamil, diltiazem, itraconazole, fluvoxamine, nefa-zodone, and erythromycin) can increase buspirone levels. Likewise, enzyme inducers such as rifampin can reduce buspirone levels significantly. Bupirone may increase blood pressure when coadministered with an monoamine oxidase inhibitor (MAOI). 

Ball, S.E. et al. (1999). Population distribution and effects on drug metabolism of a genetic variant in the 5 promoter region of CYP3A4. Clin. Pharmacol. Ther., 66, 288-94. 

Ito, K., Kusuhara, H., Sugiyama, Y., Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorption -theoretical approach, Pharm. Res. 

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