Pub. Date : 2019 Nov
PMID : 31492693
10 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Interindividual Variation in CYP3A Activity Influences Lapatinib Bioactivation. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 2 | The goal of this study was to determine the effect of CYP3A5 genotype and individual variation in CYP3A activity on the metabolic activation of lapatinib using human-relevant in vitro systems. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 3 | Further, the relative contributions of CYP3A4 and CYP3A5 to lapatinib O-debenzylation were estimated using selective chemical inhibitors of CYP3A. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 4 | Further, the relative contributions of CYP3A4 and CYP3A5 to lapatinib O-debenzylation were estimated using selective chemical inhibitors of CYP3A. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 5 | The results from this study demonstrated that lapatinib O-debenzylation and quinone imine-GSH conjugate formation were highly correlated with hepatic CYP3A activity, as measured by midazolam 1"-hydroxylation. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 6 | CYP3A4 played a dominant role in lapatinib bioactivation in all liver tissues evaluated. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 7 | These findings indicate that individual CYP3A activity, not CYP3A5 genotype alone, is a key determinant of lapatinib bioactivation and likely influences exposure to reactive metabolites. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 8 | SIGNIFICANCE STATEMENT: This study is the first to examine the effect of CYP3A5 genotype, total CYP3A activity, and CYP3A5-selective activity on lapatinib bioactivation in individual human liver tissues. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 9 | The results of this investigation indicate that lapatinib bioactivation via oxidative O-debenzylation is highly correlated with total hepatic CYP3A activity, and not CYP3A5 genotype alone. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |
| 10 | These findings provide insight into the individual factors, namely, CYP3A activity, that may affect individual exposure to reactive, potentially toxic metabolites of lapatinib. | Lapatinib | cytochrome P450 family 3 subfamily A member 4 | Homo sapiens |