Pub. Date : 2019 Mar
PMID : 30088221
9 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Effect of Fluconazole Coadministration and CYP2C9 Genetic Polymorphism on Siponimod Pharmacokinetics in Healthy Subjects. | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 2 | OBJECTIVES: The aim of this study was to assess the pharmacokinetics (PK) and safety/tolerability of siponimod in healthy subjects when coadministered with (1) the moderate cytochrome P450 (CYP) 2C9 and CYP3A inhibitor fluconazole (Study A), and (2) with three different CYP2C9 genotype variants (Study B). | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 3 | OBJECTIVES: The aim of this study was to assess the pharmacokinetics (PK) and safety/tolerability of siponimod in healthy subjects when coadministered with (1) the moderate cytochrome P450 (CYP) 2C9 and CYP3A inhibitor fluconazole (Study A), and (2) with three different CYP2C9 genotype variants (Study B). | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 4 | In Study B, the AUCs of siponimod were approximately two to fourfold greater in subjects with the CYP2C9*2/*3 and CYP2C9*3/*3 genotypes, with a minor increase in Cmax versus the CYP2C9*1/*1 genotype. | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 5 | In Study B, the AUCs of siponimod were approximately two to fourfold greater in subjects with the CYP2C9*2/*3 and CYP2C9*3/*3 genotypes, with a minor increase in Cmax versus the CYP2C9*1/*1 genotype. | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 6 | In Study B, the AUCs of siponimod were approximately two to fourfold greater in subjects with the CYP2C9*2/*3 and CYP2C9*3/*3 genotypes, with a minor increase in Cmax versus the CYP2C9*1/*1 genotype. | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 7 | CONCLUSIONS: Changes in siponimod PK, when coadministered with fluconazole at steady-state and in subjects with different CYP2C9 genotypes, indicate that the reduced CYP2C9 enzymatic activity does not affect the absorption phase of siponimod but prolongs the elimination phase. | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 8 | CONCLUSIONS: Changes in siponimod PK, when coadministered with fluconazole at steady-state and in subjects with different CYP2C9 genotypes, indicate that the reduced CYP2C9 enzymatic activity does not affect the absorption phase of siponimod but prolongs the elimination phase. | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |
| 9 | These results confirm the relevance of CYP2C9 activity on siponimod metabolism in humans. | siponimod | cytochrome P450 family 2 subfamily C member 9 | Homo sapiens |