Publication

Drug-metabolizing activity of human and rat liver, lung, kidney and intestine slices

De Kanter, R., De Jager, MH., Draaisma, AL., Jurva, JU., Olinga, P., Meijer, DKF. & Groothuis, GMM., May-2002, In : Xenobiotica. 32, 5, p. 349-362 14 p.

Research output: Contribution to journalArticleAcademicpeer-review

1. Organ-specific biotransformation was studied in human and rat liver, lung, kidney and small intestine slices and compared on a protein basis, using four model substances.

2. Deethylation of lidocaine was highest in liver slices from both man and rat, followed by the small intestine.

3. Metabolism of testosterone was highest in liver slices, but a different overall metabolic pattern was found between the different organs.

4. Lung, kidney and intestine slices prepared from human and rat organs showed mainly an unknown metabolite of 7-ethoxycoumarin identified as 4-ethoxy-2-hydroxyphenyl propionic acid (EPPA).

5. The maximal metabolism of 7-ethoxycoumarin in slices was equal with in vivo V-max in the rat.

6. Phase II metabolism of 7-hydroxycoumarin in kidney and intestinal slices was about 60% of the activity in liver slices.

7. In conclusion, organs other than the liver show a surprisingly high drug-metabolizing activity. Thus, the use of precision-cut slices of a combination of drug metabolizing organs in an in vitro test system from both animal and human origin is required for a proper systematic prediction of drug metabolism in man.

Original languageEnglish
Pages (from-to)349-362
Number of pages14
JournalXenobiotica
Volume32
Issue number5
Publication statusPublished - May-2002

    Keywords

  • IN-VITRO PHARMACOTOXICOLOGY, CYCLOSPORINE-A METABOLISM, ISOLATED HEPATOCYTES, HEPATIC MICROSOMES, 7-ETHOXYCOUMARIN METABOLISM, LIDOCAINE, CLEARANCE, KINETICS, TISSUE, TOXICITY

ID: 4022203