Combined Effect of Sodium Warfarin and Phenylbutazone

Eisen, Milton J.

doi:10.1001/jama.1964.03070010070021

Cited by 45 publications

(5 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has long been established that certain drugs will compete with warfarin for albumin binding sites, resulting in increased levels of unbound warfarin and hence potentiation of hypoprothrombinemia [3][4][5][6]. Based upon the three patients described here, researchers at Eli Lilly and Company (TRH and RLW) conducted an in vitro study to determine the extent of warfarin displacement from serum albumin by Sulofenur.…”

Section: Discussionmentioning

confidence: 99%

Hypoprothrombinemia from coadministration of sulofenur (LY 186641) and warfarin: Report of three cases

et al. 1991

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Hypoprothrombinemia from coadministration of sulofenur (LY 186641) and warfarin: Report of three cases

et al. 1991

View full text Add to dashboard Cite

“…Phenylbutazone potentiates the hypothrombinaemic effect of warfarin (Aggeler et al, 1967;Eisen, 1964;Fox, 1964;Hobbs et al, 1965;Sigg, 1956;Udall, 1975;Weiner et aI., 1965). This interaction is often cited as a typical example of interaction involving protein binding displacement.…”

Section: Interactions Affecting Plasma Protein Bindingmentioning

confidence: 99%

Drug Interactions and Clinical Pharmacokinetics

Kristensen

1976

Clinical Pharmacokinetics

View full text Add to dashboard Cite

Some drugs influence the gastro-intestinal absorption, distribution , metabolism or renal excretion of other drugs, i.e., processes involved in pharmacokinetic interactions. The clinical consequences of pharmacokinetic drug-drug interactions will be either an increase or a decrease in known therapeutic or toxic effects of the interacting drug. In order to evaluate the importance of drug interaction affecting gastro-intestinal absorption, it is necessary to distinguish between interactions which alter the rate of absorption of another drug and those which alter the amount of drug absorbed. Many drugs displace other drugs from their protein binding sites in vitro. This may cause an increase in the pharmacological effect of the displaced drug. However, much discrepancy exists between in vitro findings. In some cases, the enhanced effect only seems to be a temporary phenomenon. The degree of protein binding and the size of apparent volume of distribution (Vd) must also be taken into consideration. Perhaps the importance of interaction involving protein binding has been overemphasized. Barbiturates, glutethimide, rifampicin and phenytoin increase the rate of drug metabolism in man. The most important interactions reported are between oral anti-coagulants and barbiturates. After withdrawal of these hepatic microsomal enzyme inducing drugs, it takes 2 to 3 weeks before the rate of drug metabolism reaches the pretreatment level. In this period, risk of haemorrhage exists. Induction seems to be dose-dependent, but not all persons are inducible. Many drugs compete for the drug metabolising enzyme system in the liver and consequently some drugs inhibit the biotransformation of other drugs. The time course of these interactions depends on the pharmacokinetic properties of the drug involved, and these interactions also seem to be dose-dependent. The most important of such interactions, clinically involved the oral sulphonylurea hypoglycaemic drugs and the antiepilepic drug phenytoin. Drugs are eliminated by urinary excretion through three mechanisms: glomerular filtration, tubular reabsorption, and active tubular secretion. The most important interactions seem to be those involving competition for tubular secretion.

show abstract

“…There are also instances of untoward reactions occurring clinically in which displacement seems likely to have played a significant part. Thus the anticoagulant activity of warfarin is increased dangerously by the concurrent use of phenylbutazone (Eisen, 1964; Aggeler, O'Reilly, Leong & Kowitz, 1967). Sulphonamides enhance the hypoglycaemic action of tolbutamide (Christensen, Hansen & Kristensen, 1963 ;Biittner & Portwich, 1967).…”

mentioning

confidence: 99%

Displacement from protein binding of sulphormethoxine by phenylbutazone using in vivo dialysis in rats

McQueen¹

1969

British J Pharmacology

View full text Add to dashboard Cite

Displacement of the ultra‐long‐acting sulphonamide sulphormethoxine from binding to serum proteins by phenylbutazone has been demonstrated by in vivo dialysis in rats. The technique used involved the introduction of dialysis sacs into the peritoneal cavity. The regression line relating free to total sulphormethoxine was significantly displaced after addition of phenylbutazone to the regime although the mean level of free drug was not significantly raised. No significant effect was observed on the proportion of phenylbutazone in the free form. The range of concentrations employed corresponded to that encountered clinically. In vitro experiments with comparable concentrations of both drugs confirmed displacement of sulphormethoxine by phenylbutazone. Insignificant displacement of phenylbutazone from binding occurred. These experiments indicated the relationships between the relative affinities of sulphormethoxine and phenylbutazone for serum proteins and the extent to which mutual displacement from binding occurred.

show abstract

Combined Effect of Sodium Warfarin and Phenylbutazone

Cited by 45 publications

References 2 publications

Hypoprothrombinemia from coadministration of sulofenur (LY 186641) and warfarin: Report of three cases

Hypoprothrombinemia from coadministration of sulofenur (LY 186641) and warfarin: Report of three cases

Drug Interactions and Clinical Pharmacokinetics

Displacement from protein binding of sulphormethoxine by phenylbutazone using in vivo dialysis in rats

Contact Info

Product

Resources

About