D-glucaric acid excretion in critical care patients--comparison with 6 beta-hydroxycortisol excretion and serum gamma-glutamyltranspeptidase activity and relation to multiple drug therapy.
The incidence of increased drug metabolism activity as a consequence of multiple drug therapy at a surgical intensive care ward has been studied non-invasively by determinations of daily urinary D-glucaric acid (GA) excretion rates. Among 165 randomly selected patients, GA excretion was stimulated in 76 cases (= 46%). Exploratory data analysis showed that increases in GA excretion are primarily due to administration of barbiturates (pentobarbitone, Nembutal), miconazole (Daktar) and, to a lesser extent, neuroleptics. Surprisingly, the large number of simultaneously administered additional drugs failed to increase GA excretion. Urinary 6 beta-hydroxycortisol (6 beta-OHF) and 17-hydroxycorticosteroid (17-OHCS) excretion rates were correlated in 34 patients with GA excretion; patients not receiving known enzyme inducers showed low GA values but high 6 beta-OHF and 17-OHCS values, however, with a ratio of 6 beta-OHF/17-OHCS in the normal range. Patients receiving high dose pentobarbitone treatment failed to exhibit significantly increased 6 beta-OHF and 17-OHCS or 6 beta-OHF/17-OHCS values. Miconazole treatment resulted in a significantly increased ratio of 6 beta-OHF/17-OHCS. gamma-Glutamyltranspeptidase activity in serum showed no correlation with GA excretion (n = 91).
Heinemeyer
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Lestau
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Klaiber
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Dennhardt
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D015065:17-Hydroxycorticosteroids / Q000652:urine; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D003422:Critical Care; D004359:Drug Therapy, Combination; D005260:Female; D005937:Glucaric Acid / Q000652:urine*; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000652:urine; D007902:Length of Stay; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D008875:Middle Aged; D010424:Pentobarbital / Q000494:pharmacology; D013400:Sugar Acids / Q000652:urine*; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000097:blood*
D015065:17-Hydroxycorticosteroids; D013400:Sugar Acids; C001380:6 beta-hydroxycortisol; D008825:Miconazole; D005723:gamma-Glutamyltransferase; D010424:Pentobarbital; D005937:Glucaric Acid; D006854:Hydrocortisone