Pub. Date : 1998 Jul
PMID : 9660842
11 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | At therapeutic concentrations (steady-state plasma concentrations approximately 4 microM), nelfinavir was found to be a competitive inhibitor of only testosterone 6beta-hydroxylase (CYP3A4) with a Ki concentration of 4. | Nelfinavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 2 | At supratherapeutic concentrations, nelfinavir competitively inhibited dextromethorphan O-demethylase (CYP2D6), S-mephenytoin 4-hydroxylase (CYP2C19), and phenacetin O-deethylase (CYP1A2) with Ki concentrations of 68, 126, and 190 microM, respectively. | Nelfinavir | cytochrome P450 family 2 subfamily D member 6 | Homo sapiens |
| 3 | At supratherapeutic concentrations, nelfinavir competitively inhibited dextromethorphan O-demethylase (CYP2D6), S-mephenytoin 4-hydroxylase (CYP2C19), and phenacetin O-deethylase (CYP1A2) with Ki concentrations of 68, 126, and 190 microM, respectively. | Nelfinavir | cytochrome P450 family 2 subfamily C member 19 | Homo sapiens |
| 4 | At supratherapeutic concentrations, nelfinavir competitively inhibited dextromethorphan O-demethylase (CYP2D6), S-mephenytoin 4-hydroxylase (CYP2C19), and phenacetin O-deethylase (CYP1A2) with Ki concentrations of 68, 126, and 190 microM, respectively. | Nelfinavir | cytochrome P450 family 2 subfamily C member 19 | Homo sapiens |
| 5 | At supratherapeutic concentrations, nelfinavir competitively inhibited dextromethorphan O-demethylase (CYP2D6), S-mephenytoin 4-hydroxylase (CYP2C19), and phenacetin O-deethylase (CYP1A2) with Ki concentrations of 68, 126, and 190 microM, respectively. | Nelfinavir | cytochrome P450 family 1 subfamily A member 2 | Homo sapiens |
| 6 | The inhibitory potency of nelfinavir toward CYP3A4 suggested the possibility of in vivo inhibition of this isoform, whereas in vivo inhibition of other P450s was considered unlikely. | Nelfinavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 7 | In a one-sequence crossover study in 12 healthy volunteers, nelfinavir inhibited the elimination of the CYP3A substrate terfenadine and the carboxylate metabolite of terfenadine. | Nelfinavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 8 | The 24-hr urinary recoveries of 6beta-hydroxycortisol were reduced by an average of 27% during nelfinavir treatment, consistent with CYP3A inhibition by nelfinavir. | Nelfinavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 9 | Inhibition of CYP3A4 by nelfinavir in vitro was NADPH-dependent requiring the catalytic formation of a metabolite or a metabolic intermediate. | Nelfinavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 10 | Although incubations with nelfinavir showed a time- and concentration-dependent loss of CYP3A4 activity, the partial or complete recovery of enzyme activity upon dialysis indicated that inhibition was reversible. | Nelfinavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 11 | Collectively, these results suggest that the probable mechanism for CYP3A4 inhibition by nelfinavir is a transient metabolic intermediate or stable metabolite that coordinates tightly but reversibly to the heme moiety of the P450. | Nelfinavir | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |