Pub. Date : 2021 Apr
PMID : 33561738
6 Functional Relationships(s)Download |
Sentence | Compound Name | Protein Name | Organism |
| 1 | Physiologically based pharmacokinetic modeling of altered tizanidine systemic exposure by CYP1A2 modulation: Impact of drug-drug interactions and cigarette consumption. | tizanidine | cytochrome P450 family 1 subfamily A member 2 | Homo sapiens |
| 2 | Tizanidine is primarily metabolized by CYP1A2 and is considered a sensitive index substrate for this enzyme. | tizanidine | cytochrome P450 family 1 subfamily A member 2 | Homo sapiens |
| 3 | The physiologically based pharmacokinetic (PBPK) modeling platform Simcyp was used to evaluate the impact of CYP1A2 modulation on tizanidine exposure through drug-drug interactions (DDIs) and host-dependent habits (cigarette smoking). | tizanidine | cytochrome P450 family 1 subfamily A member 2 | Homo sapiens |
| 4 | The model was then used to carry-out DDI simulations to predict alterations in tizanidine systemic exposure when co-administered with various CYP1A2 perpetrators including competitive inhibitors (fluvoxamine, ciprofloxacin), a mechanism-based inhibitor (rofecoxib), and an inducer (rifampin). | tizanidine | cytochrome P450 family 1 subfamily A member 2 | Homo sapiens |
| 5 | Under each scenario, the PBPK model was able to capture the observed fold changes in tizanidine Cmax and AUC of tizanidine when coadministered with CYP1A2 inhibitors or inducers. | tizanidine | cytochrome P450 family 1 subfamily A member 2 | Homo sapiens |
| 6 | Under each scenario, the PBPK model was able to capture the observed fold changes in tizanidine Cmax and AUC of tizanidine when coadministered with CYP1A2 inhibitors or inducers. | tizanidine | cytochrome P450 family 1 subfamily A member 2 | Homo sapiens |