Hepatic microsomal enzyme induction and its evaluation in a clinical laboratory.
We tried to determine whether short-term treatment with alpha-methyldopa, quinidine, digoxin, diazepam or furosemide--drugs in common use in hospitals--is capable of stimulating the activity of hepatic microsomal drug-metabolizing enzymes. Glucaric acid (GA) excretion and serum activity of gamma-glutamyl transpeptidase (GGT) were used as indicators of hepatic microsomal enzyme activity. Increased GA excretion was found in 45% and increased serum GGT activity in 40% of the patients on drug treatment. Only 14.3% showed an increase in both indicators. The excretion of GA rose significantly in patients who received drugs for less than 10 days, as compared with those who received drugs for less than 10 days, whereas the percentage of high GGT values did not rise significantly with increased duration of treatment. The lack of correlation between serum GGT activity and GA excretion casts doubt on the value of GGT as a consistent indicator of microsomal enzyme induction. GA excretion, on the other hand, seems to be a dependable index of microsomal enzyme induction in response to short-term treatment with standard doses of several widely used drugs.
D000328:Adult; D000368:Aged; D003975:Diazepam / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005665:Furosemide / Q000494:pharmacology; D005937:Glucaric Acid / Q000652:urine; D006801:Humans; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology* / Q000378:metabolism; D008875:Middle Aged; D011802:Quinidine / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000097:blood*
D008750:Methyldopa; D004077:Digoxin; D005665:Furosemide; D005723:gamma-Glutamyltransferase; D011802:Quinidine; D003975:Diazepam; D005937:Glucaric Acid