Редактирование: UGT2B7 (раздел)

==Publications==

{{medline-entry
|title=Application of a physiologically based pharmacokinetic model for the prediction of mirabegron plasma concentrations in a population with severe renal impairment.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30985942
|abstract=We previously verified a physiologically based pharmacokinetic (PBPK) model for mirabegron in healthy subjects using the Simcyp Simulator by incorporating data on the inhibitory effect on cytochrome P450 (CYP) 2D6 and a multi-elimination pathway mediated by [[CYP3A4]], uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7 and butyrylcholinesterase (BChE). The aim of this study was to use this PBPK model to assess the magnitude of drug-drug interactions (DDIs) in an elderly population with severe renal impairment (sRI), which has not been evaluated in clinical trials. We first determined the system parameters, and meta-analyses of literature data suggested that the abundance of [[UGT2B7]] and the BChE activity in an elderly population with sRI was almost equivalent to and 20% lower than that in healthy young subjects, respectively. Other parameters, such as the [[CYP3A4]] abundance, for an sRI population were used according to those built into the Simcyp Simulator. Second, we confirmed that the PBPK model reproduced the plasma concentration-time profile for mirabegron in an sRI population (simulated area under the plasma concentration-time curve (AUC) was within 1.5-times that of the observed value). Finally, we applied the PBPK model to simulate DDIs in an sRI population. The PBPK model predicted that the AUC for mirabegron with itraconazole (a [[CYP3A4]] inhibitor) was 4.12-times that in healthy elderly subjects administered mirabegron alone, and predicted that the proportional change in AUC for desipramine (a [[CYP2D6]] substrate) with mirabegron was greater than that in healthy subjects. In conclusion, the PBPK model was verified for the purpose of DDI assessment in an elderly population with sRI.
|mesh-terms=* Acetanilides
* Adolescent
* Adrenergic beta-3 Receptor Agonists
* Adult
* Aged
* Aging
* Butyrylcholinesterase
* Cytochrome P-450 CYP2D6 Inhibitors
* Cytochrome P-450 CYP3A
* Cytochrome P-450 CYP3A Inhibitors
* Desipramine
* Drug Interactions
* Female
* Gemfibrozil
* Glucuronosyltransferase
* Humans
* Itraconazole
* Lorazepam
* Male
* Middle Aged
* Models, Biological
* Renal Insufficiency
* Thiazoles
* Young Adult
* Zidovudine
|keywords=drug-drug mirabegron, physiologically-based pharmacokinetic model, renal impairment, the Simcyp Simulator
|full-text-url=https://sci-hub.do/10.1002/bdd.2181
}}