Abstract
Purpose
To investigate the effects of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 and its relationship with CYP2C9 genotypes.
Methods
Twelve healthy adult men of known CYP2C9 genotype (six CYP2C9*1/*1 and six CYP2C9*1/*3) were recruited in a two-phase randomized crossover design study. The pharmacokinetics of losartan and E-3174 were measured before and after a 14-day treatment with 140 mg of silymarin three times daily.
Results
The area under the plasma concentration–time curve (AUC) of losartan increased significantly following a 14-day silymarin treatment in subjects with the CYP2C9*1/*1 genotype, but not in those with the CYP2C9*1/*3 genotype. The AUC of E-3174 decreased significantly with a silymarin pretreatment in both CYP2C9*1/*1 and the CYP2C9*1/*3 subjects. The metabolic ratio of losartan (ratio of \({\text{AUC}}_{{\text{0}} - \infty } {\text{ }}\) of E-3174 to \({\text{AUC}}_{{\text{0}} - \infty } \) of losartan) decreased significantly after a 14-day treatment with silymarin in individuals with the CYP2C9*1/*1 genotype (p < 0.05), but not in those with the CYP2C9*1/*3 genotype (p = 0.065).
Conclusion
Silymarin inhibits the metabolism of losartan to E-3174, with the magnitude of the interaction differing in individuals with different CYP2C9 genotypes.
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Acknowledgements
The study was supported by a grant from Madaus AG, Cologne, Germany.
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Han, Y., Guo, D., Chen, Y. et al. Effect of silymarin on the pharmacokinetics of losartan and its active metabolite E-3174 in healthy Chinese volunteers. Eur J Clin Pharmacol 65, 585–591 (2009). https://doi.org/10.1007/s00228-009-0624-9
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DOI: https://doi.org/10.1007/s00228-009-0624-9