Terfenadine metabolism

Jurima-Romet, M., Crawford, K. et al. (1994). Terfenadine metabolism in human liver. In vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab. Dispos., 22(6), 849-57. 

Von Moltke LL, Greenblatt DJ, Duan SX, et al. Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin reuptake inhibitor antidepressants Relations to pharmacokinetic interactions in vivo. / Clin Psychopharmacol. 1996 16 104-112. 

Jurima-Romet, M. Crawford, K. Cyr, T. Inaba, T. Terfenadine metabolism in human liver. In vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab.Dispos., 1994, 22, 849—857 [extracted metabolites microsomal incubations rat column temp 35 LOQ 92 nM] von Moltke, L.L. Greenblatt, D.J. Duan, S.X. Harmatz, J.S. Shader, R.I. In vitro prediction of the terfenadine-ketoconazole pharmacokinetic interaction. J.Clin.Pharmacol., 1994, 34, 1222—1227 [clomipramine (IS) microsomal incubations]... 

Kivisto, K.T., RJ. Neuvonen, and U. Klotz (1994). Inhibition of terfenadine metabolism Pharmacokinetic and pharmacodynamic consequences. Clin. Pharmacokinet. 27, 1-5. 

Pohjola-Sintonen S, ViitasaloM, ToivonenL,NeuvonenP. Itraconazole prevents terfenadine metabolism and increases risk of torsades de pointes ventricular tachycardia. EurJClinPhar-macol ( 993) 45, 191-3. 

A study in 16 healthy men given zafirlukast 160 mg twice daily for 16 days with terfenadine 60 mg twice daily on days 8 to 16 found that the mean maximum serum levels and AUC of zafirlukast were reduced by 70% and 60%, respectively. There was a small, non-significant reduction in the terfenadine AUC and serum levels. A study in 8 healthy subjects given zafirlukast 160 mg twice daily with terfenadine 60 mg twice daily for 8 days found that the AUC of terfenadine and the QTc interval were not significantly increased with concurrent use, despite the fact that zafirlukast appears to inhibit CYP3A4 in vitro, the major enzyme involved in terfenadine metabolism. The reduction in zafirlukast serum levels would be expected to reduce its antiasthmatic effects, but this needs assessment. If both drugs are given be alert for a reduced response to zafirlukast. 

Kivisto KT, Neuvonen PJ, Klolz U (1994) Inhibition of terfenadine metabolism pharmacokinetic and pharmacodynamic consequences. Clin Pharma-cokinet27 l 5... 

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