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Dear All,
Can anybody give some references or information on the fate of cyp3a4
turnover or activity in hepatic impairment? I am asking in relation
to predict clearance of a compound (that is 90% metabolized by
cyp3a4) at various levels of hepatic impaired subjects.
Thanks for your help.
Ayyappa
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Ayappa,
Although there is broad belief that there is differential alterations
CYP450 proteins in patients with liver disease ( George J et al 1995,
Hepatology; Rodighiero V, 1999, Clin pharmacokinet), CYP3A4
expression (as measured by MEGX AUCs) did not appear to be
consistently affected by the degree of hepatic impairment (Sarapa et
al , 2005, Eur J clin Pharmacol).
All the best!
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The following message was posted to: PharmPK
Ayyappa,
Some studies on Egyptian patients with liver cirrhosis demonstrated
changes in 3A4 activity as reflected by change in MEGX serum
concentration as well as change in urinary ratio of 6 beta
hydroxycortisol/cortisol in relation to different pathological stages
of liver cirrhosis.
Please revise the following references:
1- ELDesoky ES, et al. Assessment of liver function by the MEGX test
in patients with schistosomiasis and cirrhosis. Clinical Biochemistry
1999; 32: 207-221.
2- ELDesoky ES, Study of the urinary ratio of 6 - beta
hydroxycortisol/cortisol as a biomarker of cyp3A4 activity in Egyptian
patients with chronic liver diseases. Drug Target Insights 2006; 2:
157-164
Best regards,
Ehab ELDesoky
Professor of pharmacology
Assiut University, Egypt
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