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Effect of long term alcohol consumption on the half life of tetracycline and doxycycline in man

ABSTRACT 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.

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    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 · 13.32 Impact Factor
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    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.
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    ABSTRACT: The biotransformation of amitriptyline (AMT) during steady state conditions was studied in plasma and urine from 11 nonalcoholic and 10 alcoholic depressive inpatients treated with oral AMT. The 2 groups of patients had a different pattern of biotransformation. The Demethylation of AMT was lower in alcoholic than in nonalcoholic depressive patients, and conjugation and hydroxylation of AMT were also more marked in the former group. The results may be of clinical relevance since the conjugates of AMT are inactive.
    European Journal of Clinical Pharmacology 02/1983; 24(5):615-21. DOI:10.1007/BF00542210 · 2.70 Impact Factor
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