OBJECTIVE: The effects of CYP2C9*1/*3 and *1/*13 genotypes were evaluated on the pharmacokinetics of losartan and its active metabolite, E-3174, in Korean subjects. METHODS: Losartan (50 mg) was administered in 43 Korean volunteers with different CYP2C9 genotypes (CYP2C9*1/*1, *1/*3 and *1/*13). Losartan and E-3174 levels in the plasma and urine were analyzed by HPLC using fluorescence. RESULTS: The CYP2C9*1/*13 subjects showed lower oral clearance (p < 0.001) and greater AUC0-∞ (p < 0.01) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.001) of E-3174 than the CYP2C9*1/*1 subjects, but AUC0-∞ of E-3174 was not different. The CYP2C9*1/*3 subjects showed lower oral clearance (p < 0.001) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.01) of E-3174 than the CYP2C9*1/*1 subjects. However, AUC0-∞ of losartan was greater in CYP2C9*1/*3 subjects than in CYP2C9*1/*1, but these results were not significant (p < 0.05, but statistical power < 0.8). In addition, AUC0-∞ of E-3174 was not different. There were no significant differences in pharmacokinetic parameters between the CYP2C9*1/*13 and CYP2C9*1/*3 subjects. CONCLUSION: These results suggest that CYP2C9*1/*3 and CYP2C9*1/*13 are similarly associated with decreased formation of E-3174 from losartan, but the clinical effects of losartan may not be reduced by CYP2C9*1/*3 and CYP2C9*1/*13.
OBJECTIVE: The effects of CYP2C9*1/*3 and *1/*13 genotypes were evaluated on the pharmacokinetics of losartan and its active metabolite, E-3174, in Korean subjects. METHODS:Losartan (50 mg) was administered in 43 Korean volunteers with different CYP2C9 genotypes (CYP2C9*1/*1, *1/*3 and *1/*13). Losartan and E-3174 levels in the plasma and urine were analyzed by HPLC using fluorescence. RESULTS: The CYP2C9*1/*13 subjects showed lower oral clearance (p < 0.001) and greater AUC0-∞ (p < 0.01) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.001) of E-3174 than the CYP2C9*1/*1 subjects, but AUC0-∞ of E-3174 was not different. The CYP2C9*1/*3 subjects showed lower oral clearance (p < 0.001) of losartan and higher Cmax (p < 0.01) and longer half-life (p < 0.01) of E-3174 than the CYP2C9*1/*1 subjects. However, AUC0-∞ of losartan was greater in CYP2C9*1/*3 subjects than in CYP2C9*1/*1, but these results were not significant (p < 0.05, but statistical power < 0.8). In addition, AUC0-∞ of E-3174 was not different. There were no significant differences in pharmacokinetic parameters between the CYP2C9*1/*13 and CYP2C9*1/*3 subjects. CONCLUSION: These results suggest that CYP2C9*1/*3 and CYP2C9*1/*13 are similarly associated with decreased formation of E-3174 from losartan, but the clinical effects of losartan may not be reduced by CYP2C9*1/*3 and CYP2C9*1/*13.
Authors: Michael T Eadon; Judith Maddatu; Sharon M Moe; Arjun D Sinha; Ricardo Melo Ferreira; Brent W Miller; S Jawad Sher; Jing Su; Victoria M Pratt; Arlene B Chapman; Todd C Skaar; Ranjani N Moorthi Journal: Kidney360 Date: 2022-02-24
Authors: Sara L Van Driest; Lynn A Sleeper; Bruce D Gelb; Shaine A Morris; Harry C Dietz; Geoffrey A Forbus; Elizabeth Goldmuntz; Arvind Hoskoppal; Jeanne James; Teresa M Lee; Jami C Levine; Jennifer S Li; Bart L Loeys; Larry W Markham; Josephina A N Meester; Seema Mital; Jonathan D Mosley; Aaron K Olson; Marjolijn Renard; Christian M Shaffer; Angela Sharkey; Luciana Young; Ronald V Lacro; Dan M Roden Journal: J Pediatr Date: 2020-07 Impact factor: 4.406