Warfarin clearance

Sulfaphenazole is perhaps the most potent and selective inhibitor of CYP2C9 (71). The mode of inhibition is via ligation to the heme iron of CYP2C9. Sulfaphenazole is a very commonly used in vitro diagnostic inhibitor for CYP2C9 activity, but it has been used in vivo for this purpose. The azole antifungal fluconazole also inhibits CYP2C9, and a series of studies has demonstrated the relationship between in vitro values and the in vivo effect on warfarin clearance (72-74). 

Alcoholics can drink ethanol in amounts large enough (200 g) to inhibit warfarin clearance as an acute effect. However, daily consumption of ethanol for a period of 3 weeks in the form of wine taken with meals in moderate amounts (28 g/day) or even in liberal amounts (56 g/day) had no effect on the hypoprothrombinemia induced by warfarin (256). 

Erythromycin Potentiation possible (164,165) Reduced warfarin clearance (166) Monitor INR... 

Watt AH, Stephens MR, Buss DC, Routledge PA. Amiodarone reduces plasma warfarin clearance in man. Br J Clin Pharmacol 1985 20(6) 707-9. 

Although poorly studied, some evidence shows that the CYP2C9 5 and 6 alleles may be of importance to warfarin clearance [24]. Using losartan as an in vivo test of CYP2C9 activity, patients who had the 5 allele were found to have impaired losartan oxidation compared with patients who had the 1 however, the number of patients who had variant genotypes was small. In vitro data support that 5, 6, 8, and 11 alleles all have reduced activity compared with 1. The clinical relevance of these changes has not been determined. 

In -4—5% of patients taking zileuton, there is an elevation in hepatic transaminases, generally within the first 2 months of therapy. Zileuton decreases the steady-state clearance of theophylline, substantially increasing its plasma concentrations. Zileuton also decreases warfarin clearance. 

TakahashiH, Kashima T, Kimura S, MurataN, TakabaT, Iwade K, Abe T, Tainaka H, Yas-umori T, Echizen H. Pharmacokinetic interaction between warfarin and a uricosuric agent, bucolome application of in vitro approaches to piedictii in vivo reduction of ( ) warfarin clearance. DmgMetab Dispos (1999) 27, 1179-86. 

Desmond PV, MashfordML, Harman PJ, Morphett BJ, Breen KJ, Wang YM. Decreased oral warfarin clearance after ranitidine and cimetidine. Clin Pharmacol Ther (1984) 35, 338-41. 

Mu, Y, J. Zhang, S. Zhang, et al. 2006. Traditional Chinese medicines wu wei zi (Schisandra chinensis Baill.) and gan cao (Glycyrrhiza ura-lensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats.). Pharmacol. Exp. Ther. 316(3) 1369-1377. 

Influences warfarin clearance and is also associated with need for decreased maintenance dosages... 

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