Impairment of Drug Metabolism in Man by Allopurinol and Nortriptyline

Es, Vesell; Gt, Passananti; Fe, Greene

doi:10.1056/nejm197012312832703

Cited by 164 publications

(53 citation statements)

References 14 publications

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“…Nortriptyline was also shown to impair the metabolism of dicoumarol and antipyrine (Vesell et al, 1970), whereas Vesell et al (1975) and Pond et al (1975) failed to find any alteration of drug metabolism. On the other hand, no induction of cytochrome P450 and related monoxygenase activities was noted after treatment of rats with nortriptyline (Vesell etal., 1975).…”

Section: Discussionmentioning

confidence: 95%

Induction of drug‐metabolizing enzymes by tricyclic antidepressants in human liver: characterization and partial resolution of cytochromes P‐ 450.

Cresteil¹,

Celier²,

Kremers³

et al. 1983

Brit J Clinical Pharma

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1 Drug-metabolizing enzyme activities were determined in liver microsomes from six kidney-transplant donors, one tricyclic antidepressant-treated and five untreated donors. 2 The tricyclic antidepressant treatment modifies neither the overall cytochrome P-450 content of the liver, nor enzymatic activities of 4-nitroanisole demethylase, aniline hydroxylase, epoxide hydrolase and glutathione S-transferase. 3 Only benzphetamine and ketotifen demethylation and conjugation of bilirubin with UDP-glucuronic acid are markedly augmented (more than two-fold). 4 Separation of the different cytochrome P450 fractions on a DEAE cellulose column indicates a modification of the elution pattern: the fraction increased by tricyclic antidepressants is responsible for the enhanced monooxygenase activity towards benzopyrene and benzphetamine.

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Section: Discussionmentioning

confidence: 95%

Induction of drug‐metabolizing enzymes by tricyclic antidepressants in human liver: characterization and partial resolution of cytochromes P‐ 450.

Cresteil¹,

Celier²,

Kremers³

et al. 1983

Brit J Clinical Pharma

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“…Drug-induced microsomal enzyme inhibition has received less attention, though the implication that drugs may reduce metabolizing capacity might be of even greater importance in therapeutics. Vesell et al (1970) observed that allopurinol consistently reduces the rates of antipyrine and bishydroxycoumarin elimination in man and prompted us to perform the present studies. In the volunteer experiments considered as a whole, treatment with allopurinol for one month did not produce any significant changes in either phenylbutazone or warfarin kei.…”

Section: Patient Studiesmentioning

confidence: 92%

Influence of allopurinol on drug metabolism in man

Rawlins

Smith

1973

British J Pharmacology

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Summary Elimination rates of phenylbutazone and warfarin after single oral doses in human volunteers, and steady‐state plasma concentrations of these drugs in patients have been measured before, during and after administration of allopurinol. Allopurinol, in usual clinical doses, had no significant influence on the elimination rate of either drug in the group of volunteers as a whole although in a few individuals an apparent inhibitory effect was observed. No significant changes in the steady‐state plasma concentrations of either phenylbutazone or warfarin were observed in patients during the administration of allopurinol. It is concluded that although allopurinol may have an apparent inhibitory effect on drug elimination in a few individuals, its administration to most patients on anticoagulant therapy is unlikely to alter dose requirements.

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Section: Drugs Causing Inhibition Of Metabolismmentioning

confidence: 99%

“…Tricyclic antidepressants, such as amitriptyline and nortryptiline, may increase the half-life of oral anticoagulants 204,205 . However, considerable interindividual differences may be found 206 .…”

Section: Drugs Causing Inhibition Of Metabolismmentioning

confidence: 99%

“…Allopurinol may enhance warfarin effect by inhibition of its metabolism 150,151 . However, a number of case reports have demonstrated an inconsistent effect of allopurinol on warfarin therapy 152,153,154 .Phenylbutazone stereoselectively inhibits warfarin metabolism 96 . It was demonstrated that the drug inhibits the metabolism of S-warfarin (more potent enantiomer) while increasing the rate of elimination of R-warfarin.…”

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confidence: 99%

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Interactions of Warfarin

Rehulková¹

2001

BIOMED PAP

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In this article, the author reviews and updates the basis of interactions with warfarin, illustrated with appropriate examples. The interactions with drugs, medicinal herbs and foods are summarised. 28Cholestyramine binds vitamin K in the gut, thus preventing its absorption 18 . It also decreases the absorption and may interrupt the enterohepatic recirculation of warfarin, resulting in a reduced anticoagulant effect 19,20 .Colestipol does not affect the absorption of warfarin. When colestipol is administered with warfarin, no depressant effects on blood levels are seen 21 . Drugs affecting receptor sensitivityEstrogens increase the synthesis of various clotting factors and may thus reduce the effect of anticoagulants 22, 23 . Oral contraceptives increase clotting factor concentrations and inhibit warfarin metabolism. The net effect depends on balance between these factors. Oral contraceptives are generally contraindicated in most patients taking warfarin since they are trombogenic 1, 24 .Steroids with anabolic or androgenic properties, such as oxymetholone 25, 26, 27 , stanozolol 28, 29 and danazol 30, 31, 32 , may potentiate the action of warfarin allegedly by reducing clotting factor synthesis. The 17-alpha-alkylated steroids appear to be more likely to induce this reaction than the non-substituted steroids 25, 26, 27, 33 . However, there has been a report of topically applied testosterone, which does not have 17-alpha-alkyl substituent, enhancing warfarin 34 .Diuretics may antagonise the action of warfarin by two pharmacodynamic mechanisms 18 : (a) patients in cardiac failure have impaired clotting factor synthesis due to hepatic congestion -correction of this state leads to increased clotting factor synthesis; (b) diuretics also reduce the plasma volume producing an increased concentration of clotting factors which may alter the anticoagulant effect of warfarin 35 . Chlorthalidone 36 and spironolactone 35 have both been associated with a reduction of warfarin activity probably as a consequence of diuresis concentrating the circulating clotting factors. Bumetanide, furosemide and thiazides appear to have no effect on warfarin 23 .Certain cephalosporines, such as cefotetan, cefamandole, cefoperazone, or moxalactam may cause marked hypoprothrombinemia and/or prolonged bleeding time at concurrent use with warfarin 38, 39, 40, 41 . The main mechanism of interaction consists in decreasing synthesis of vitamin K-dependent clotting factors.Clofibrate may potentiate warfarin action, probably by altering receptor sensitivity 23, 37 . Although clofibrate displaces warfarin from albumin binding sites this does not appear to be a principal mechanism of the interaction 42 .Drugs altering thyroid function may affect anticoagulant control, since rates of synthesis and degradation of clotting factors are dependent on thyroid function 7 . Thyroid compounds do enhance the activity of oral anticoagulants by increased metabolism of clotting factors 12 . Dextrothyroxine increases the anticoagulant effect of warfarin ...

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Impairment of Drug Metabolism in Man by Allopurinol and Nortriptyline

Cited by 164 publications

References 14 publications

Induction of drug‐metabolizing enzymes by tricyclic antidepressants in human liver: characterization and partial resolution of cytochromes P‐ 450.

Induction of drug‐metabolizing enzymes by tricyclic antidepressants in human liver: characterization and partial resolution of cytochromes P‐ 450.

Influence of allopurinol on drug metabolism in man

Interactions of Warfarin

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