ADMET and DMPK, Vol. 4 No. 2, 2016.
Original scientific paper
https://doi.org/10.5599/admet.4.2.210
Metabolism of six CYP probe substrates in fetal hepatocytes
Abdul Naveed Shaik
orcid.org/0000-0002-3672-2246
; Center for Liver Research and Diagnostics, Owaisi Research Center, Deccan College of Medical Sciences, Hyderabad, TS, India
Sandeep Kumar Vishwakarma
; Center for Liver Research and Diagnostics, Owaisi Research Center, Deccan College of Medical Sciences, Hyderabad, TS, India
Aleem Ahmed Khan
; Center for Liver Research and Diagnostics, Owaisi Research Center, Deccan College of Medical Sciences, Hyderabad, TS, India
Abstract
Cytochrome P-450 (CYP) are the most common drug metabolizing enzymes and are abundantly expressed in liver apart from kidney, lungs, intestine, brain etc. Their expression levels change with physiological conditions and disease states. The expression of these CYPs is less in human foetus and neonates compared to adults, which results in lower clearance of xenobiotics in infants and neonates compared to adults. Hepatocytes are the cells which are largely used to study these CYPs. We have isolated hepatocytes from aborted foetus to study the metabolism of six probe substrates: phenacetin, diclofenac, S-mephenytoin, dextromethorphan, nifedipine and testosterone. The results obtained show the expression of various CYPs (CYP1A2, CYP2C19, CYP2C9, CYP2D6, and CYP3A4) in human foetus and their involvement in metabolism of CYP probe substrates.
Keywords
Fetal metabolism; CYP (Cytochrome-P450); hepatocytes; metabolic stability; HPLC; dextromethorphan; diclofenac; S-mephenytoin; nifedipine; testosterone
Hrčak ID:
160635
URI
Publication date:
29.6.2016.
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