In:
Drug Metabolism and Personalized Therapy, Walter de Gruyter GmbH, Vol. 32, No. 4 ( 2017-12-20)
Kurzfassung:
For estimation of fractions metabolized (fm) by different hepatic recombinant human CYP enzymes (rhCYP), calculation of inter-system extrapolation factors (ISEFs) has been proposed. Methods: ISEF values for CYP1A2, CYP2C19 and CYP3A4/5 were measured. A CYP2C9 ISEF was taken from a previous report. Using a set of compounds, fractions metabolized by CYP enzymes (fm,CYP) values calculated with the ISEFs based on rhCYP data were compared with those from the chemical inhibition data. Oral pharmacokinetics (PK) profiles of midazolam were simulated using the physiologically based pharmacokinetics (PBPK) model with the CYP3A ISEF. For other CYPs, the Results: - Conclusions: The rhCYP data with the measured ISEFs provided reasonable calculation of fm,CYP3A4 values, showing slight over-estimation compared to chemical inhibition.
Materialart:
Online-Ressource
ISSN:
2363-8915
,
2363-8907
DOI:
10.1515/dmpt-2017-0024
Sprache:
Unbekannt
Verlag:
Walter de Gruyter GmbH
Publikationsdatum:
2017
ZDB Id:
2822040-7
SSG:
15,3
