Most ARBs are metabolized by cytochrome P4502C9 (CYP2C9), one of the major isoforms of the cytochrome P450 in human liver microsome. It converts losartan to its pharmacologically active metabolite EXP-3174 (E-3174). Other ARBs such as telmisartan and olmesartan are innate to CYP2C9, whereas candesartan and valsartan are metabolized by it to pharmacologically inactive metabolites. Maximal concentration of the drug is reached two hours post administration. Fourteen percent of the orally administered medication is converted to E-3174, which is 10 to 40 fold more potent than losartan. The pharmacokinetics of losartan and E-3174 are linear, dose dependent and do not change after repetitive administration. The CYP2C9 gene has three main polymorphic variations caused by single nucleotide polymorphism; the most common allele is CYP2C9*1 (Arg144 Ile359), and the two less common CYP2C9*2 (Cys 144Ile359) and CYP2CP*3 (Arg144Leu359) that code for an enzyme with decreased activity. The oxidation of losartan is decreased 2,3 and 40 fold in individuals genotyped as CYP2C9*1*3, CYP2C9*2*3 and CYP2C9*3*3 compared to individuals genotyped as CYP2C9*1*1.CYP2C9*3 was found to influence losartan's metabolism more than does CYP2C9*2.