Elimination of the bacteriostatics tetracycline and doxycycline was compared in patients on long-term alcohol consumption to that in healthy controls. The half-life of doxycycline but not that of tetracycline was significantly shorter in alcoholics than in controls and in some patients the serum concentration of doxycycline decreased below the generally accepted minimum therapeutic concentration when dosed once daily. So, the dosing twice daily might be indicated especially if additional inducing drugs are used.
[Show abstract][Hide abstract] ABSTRACT: Monooxygenase enzymes are involved in the biotransformation of drugs and of environmental carcinogens. The activity of 7-ethoxycoumarin 0-deethylase and associated NADPH-cytochrome c reductase was determined in 9000 g supernatant from bioptically obtained liver specimens from patients with various liver diseases in order to study in vitro drug metabolising capacity. Monooxygenase and reductase activity was significantly higher in the livers of 21 patients with alcoholic liver disease (fatty liver, alcoholic hepatitis, cirrhosis of the liver) than in 22 normal controls or in six patients with chronic active hepatitis. The raised activity of drug-metabolising enzymes obtained from alcoholics with liver damage differs from normal values found in five alcoholics without liver disease. Both groups were comparable in respect to the amount of alcohol consumed and duration of abuse. A strikingly low monooxygenase activity was observed in eight patients with cirrhosis of the liver and ascites, with, however, no apparent effect on reductase activity. The results show that alcoholic liver disease is associated with enhanced monooxygenase and reductase activity, but alcoholism, per se, is not. This rise of drug-metabolising enzyme activity could lead to selectively increased rates of biotransformation in patients with alcoholic liver damage.
Gut 09/1979; 20(8):666-72. DOI:10.1136/gut.20.8.666 · 14.66 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several conflicting observations in the literature raised considerable doubt about the metabolic fate of doxycycline, which, like other tetracyclines, has been claimed to be metabolically inert. A double liquid chromatographic approach was used in an attempt to demonstrate the polar metabolites and/or conjugates in excreta of human volunteers who ingested the drug. Both ion-exchange and reversed-phase chromatography failed to reveal significant by-products in urine and feces, except for minor amounts of 4-epidoxycycline. In addition, enzymatic hydrolysis procedures did not present any evidence of the conjugates. Thus, the different excretion behavior of doxycycline, compared to other analogs, cannot be explained in terms of increased metabolism.
[Show abstract][Hide abstract] ABSTRACT: 1 The kinetics of doxycycline were studied in well nourished and undernourished male subjects. 2 The area under the curve after an intravenous dose was reduced and total body clearance was significantly elevated with a shorter/beta-phase half life of the drug in undernourished subjects. 3 The percentage of total drug excreted in urine in 48 h and renal clearance of the drug were similar in both groups. 4 Plasma protein binding was significantly reduced and gamma-glutamyltransferase levels tended to be higher in the undernourished as compared to normals. 5 Increased total body clearance of the drug appeared therefore to be due to higher metabolism of drug in undernourished subjects. This increased metabolism is probably due to lower protein binding of the drug and/or induction of drug metabolism. 6 Plasma Cmin concentrations of doxycycline determined at steady state were lower in undernourished subjects. However, they were within the therapeutic range. 7 The observed alterations in kinetics of doxycycline therefore do not warrant a change in dosage regimen in undernourished subjects.
British Journal of Clinical Pharmacology 01/1983; 14(6):785-9. DOI:10.1111/j.1365-2125.1982.tb02037.x · 3.88 Impact Factor
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