CYP3A4, inhibition

Carbamazepine may interact with other drugs by inducing their metabolism. Valproic acid increases concentrations ofthe 10,11-epoxide metabolite without affecting the concentration of carbamazepine. The interaction of erythromycin and clarithromycin (CYP3A4 inhibition) with carbamazepine is particularly significant. 

CYP3A4 inhibition issue purple, toxicity issue). 

AUC of eletriptan 3- and 6-fold, 2- and 4-fold, 2- and 3-fold, and 1.4- and 2-fold, respectively. Do not use eletriptan within 72 hours of taking drugs that have demonstrated potent CYP3A4 inhibition. 

CYP2D6 inhibition CYP2E1 inhibition CYP3A4 inhibition (BFC substrate) CYP3A4 inhibition (BzRes substrate)... 

Variety Daidzin Genistin Daidzein Genistein Total Free CYP3A4 inhibition... 

Paine MF, Criss AB, Watkins PB. Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding properties. Drug Metab Dispos 2004 32(10) 1146-1153. 

A more interesting comparison is that of marketed chugs and pharmaceutical company compounds. There is a particularly dramatic difference in the incidence of CYP3A4 inhibition (Fig. 4E). Typical pharmaceutical company compounds are very much more inhibitory to CYP3A4 than are marketed drugs. 

Isoherranen N, Kunze KL, Allen KE, et al. Role of itraconazole metabolites in CYP3A4 inhibition. Drug Metab Dispos 2004 32(10) 1121-1131. 

CYP3A4 Inhibition Amiodarone, clarithromycin, erythromycin, cimetidine, cyclosporine, fluoxetine fluvoxamine, itraconazole, ketoconazole, nefazodone, verapamil, diltiazem HIV antivirals delaviridine, indanavire, nelfmavire, ritonavire, sequinavire Atorvastatin Lovastatin Simvastatin ... 

Drugs that inhibit CYP3A4 inhibit the clearance of terfenadine, an antihistamine that can prolong the QTC interval. This can cause potentially dangerous interactions. In a double-blind, placebo-controlled study of the effect of nefazodone (600 mg/day for 1 week) on the pharmacokinetics of terfenadine (120 mg/day for 14 days) and another antihistamine, loratadine (20 mg/day for 14 days), in 67 healthy volunteers, nefazodone significantly reduced the clearance of terfenadine and prolonged the mean QTC interval (27). In addition, nefazodone produced a similar but smaller decrease in the clearance of loratadine and combined treatment also significantly increased the QTC interval. This effect of nefazodone on... 

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. 

GRAPEFRUIT JUICE ERLOTINIB Markedly t plasma concentrations of erlotinib (t AUC, t maximum concentration). Likely to cause toxic effects of erlotinib Due to inhibition of metabolism of erlotinib by grapefruit juice as CYP3A4 inhibition is known to result in a 2.1-fold T in erlotinib exposure Monitor for toxic effects of erlotinib... 

The starting dataset used to develop the 3D quantitative structure property relationship (3D-QSPR) model consisted of 370 commercially available compounds. Activity data and 2D structures were retrieved from the Cerep database [18]. Inhibition of CYP 3A4 was reported as inhibition of the formation of 6y9-hydroxy-tes-tosterone [19]. Ketoconazole was used as reference compound so that all values are expressed as percentages. The log of the normalized CYP3A4 inhibition per-... 

Decker CJ, Laitinen LM, Bridson GW, Raybuck SA, Tung RD, Chaturvedi PR. Metabolism of amprenavir in liver microsomes role of CYP3A4 inhibition for drug interactions. J Pharm Sci 1998 87(7) 803-7. 

Riley RJ, Parker AJ, Trigg S, Manners CN. development of a generalized, quantitative physicochemical model of CYP3A4 inhibition for use in early drug discovery. Pharm Res 2001 18 652-5. 

Takeshita, A., Taguchi, M., Koibuchi, N., and Ozawa, Y. (2002) Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic receptor) in the mechanism of CYP3A4 inhibition by xenobiotics. J. Biol. Chem. 277, 32453-32458. 

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