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1. The metabolism of 50 microM [3-14C] coumarin has been studied in a panel of 12 human liver microsomal samples of known P450 isoenzyme profile. 2. [3-14C] coumarin was metabolized by human liver microsomes to various polar products including 3-, 4- and 7-hydroxycoumarins (3-HC, 4-HC and 7-HC) 6,7-dihydroxycoumarin (6,7-DiHC), o-coumaric acid (o-CA), o-hydroxyphenyl-acetaldehyde (o-HPA), o-hydroxyphenylethanol (o-HPE), o-hydroxyphenylacetic acid (o-HPAA) and o-hydroxyphenylpropionic acid (o-HPPA) and to product(s) that bind covalently to microsomal proteins. 3. For all 12 subjects, mean rates of [3-14C] coumarin metabolism to total polar products (metabolism to all products except product(s) covalently bound to microsomal proteins), 7-HC, the 3-hydroxylation pathway (sum of 3-HC, o-HPA, o-HPE and o-HPAA), o-HPPA, 6,7-DiHC and covalent binding were 1420, 1230, 73.8, 52.5, 9.5 and 4.8 pmol/min/mg protein respectively. 4. Marked interindividual differences in [3-14C] coumarin metabolism to total polar products (30-fold variation) and 7-HC (2250-fold variation) were observed. 5. Good correlations were observed between [3-14C] coumarin metabolism and total polar products, 7-HC, o-HPPA and 6,7-DiHC, but not to 3-hydroxylation pathway products and levels of 2A6 and 2B6 in human liver microsomes. 6. [3-14C] coumarin metabolism to any polar products did not correlate with levels of 1A2, 2C8, 2C9, 2E1, 3A3/4 and 4A1 in human liver microsomes.
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
March 1992,
Xenobiotica; the fate of foreign compounds in biological systems,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
October 1967,
Biochimica et biophysica acta,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
April 1991,
Xenobiotica; the fate of foreign compounds in biological systems,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
February 1971,
Canadian journal of biochemistry,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
January 2007,
Chemical research in toxicology,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
April 1980,
Xenobiotica; the fate of foreign compounds in biological systems,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
February 1995,
Xenobiotica; the fate of foreign compounds in biological systems,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
September 1991,
Biochemical pharmacology,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
February 1987,
The Journal of pharmacy and pharmacology,
M L van Iersel, and
C J Henderson, and
D G Walters, and
R J Price, and
C R Wolf, and
B G Lake
January 1974,
Steroids,
