In Vitro Method for Assessing Hepatic Drug Metabolism

We investigated an in vitro metabolic test using rat liver biopsy samples by TLC-autoradioluminography (ARLG), with a view to developing a method to rapidly assess the drug metabolizing activities of individual patients.Drug metabolizing activity was measured in liver biopsy samples collected from r...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 1997/01/15, Vol.20(1), pp.1-5
Main Authors: OKUYAMA, Mitsunobu, INOUE, Chieko, AIJIMA, Keiko, NAKAMURA, Yachiyo, KABURAGI, Takayuki, SHIGEMATSU, Akiyo
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biopsy
Cimetidine - pharmacology
Cytochrome P-450 Enzyme System - physiology
drug interaction
drug metabolism
Female
General pharmacology
Liver - metabolism
Liver - pathology
liver biopsy
Male
Medical sciences
Pharmaceutical Preparations - metabolism
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Phenobarbital - pharmacology
Rats
Rats, Wistar
Sex Factors
TLC-autoradioluminography
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Summary:We investigated an in vitro metabolic test using rat liver biopsy samples by TLC-autoradioluminography (ARLG), with a view to developing a method to rapidly assess the drug metabolizing activities of individual patients.Drug metabolizing activity was measured in liver biopsy samples collected from rats in four groups : a female control group, male control group, phenobarbital (PB)-administered male group and cimetidine (CM)-administered male group.The productivity of metabolites of 7-ethoxycoumarin (7-EC), debrisoquine (DB) and diazepam (DZ), respectively, was lower in the female control group than in the male control group, but there were no differences in the productivity of metabolites of 5-fluorouracil (5-FU) and tolbutamide (TB), respectively, between the male and female control groups. Those of 7-EC, TB and DZ were higher in the PB-administered group than in the male control group, but those of DB did not differ between these two groups. Those of 5-FU, 7-EC, TB, DB and DZ were lower in the CM-administered group than in the male control group.Using TLC-ARLG, we could detect drug metabolites in rat liver biopsy samples in a relatively short time span at low concentrations similar to those in vivo. We could also measure drug metabolizing activity in cases with and without the involvement of cytochrome P450. When applied in clinical metabolic tests, TLC-ARLG is expected to be useful for assessing the drug metabolizing activities of patients.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.20.1