Warfarin protein binding

Sands CD, Chan ES, Welty TE. Revisiting the significance of warfarin protein-binding displacement interactions. Ann Pharmacother (2002) 36, 1642-4. 

Slattery JT, Levy G. Ticiynafen effect on warfarin protein binding in human serum. J Pharm... 

The administration of cloflbrate to a patient taking warfarin will potentiate the anticoagulant effect of warfarin by displacing It from Its protein binding site (7). This Interaction will cause... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

Generally, plasma protein binding of acidic drugs (e.g., warfarin, pheny-toin) is decreased in CKD, whereas binding of basic drugs (e.g., quinidine, lidocaine) is usually normal or slightly decreased or increased. 

Distribution - Valproic acid is rapidly distributed. Volume of distribution of total or free valproic acid is 11 or 92 L/1.73 m, respectively. Valproic acid has been detected in CSF (approximately 10% of total concentrations) and milk (about 1% to 10% of serum concentrations). Therapeutic range is commonly considered to be 50 to 100 mcg/mL of total valproate. The plasma protein binding of valproate is concentration-dependent. Protein binding of valproate is reduced in the elderly, in patients with chronic hepatic diseases, in patients with renal impairment, and in the presence of other drugs (eg, aspirin). Conversely, valproate may displace certain protein-bound drugs (eg, phenytoin, carbamazepine, warfarin, tolbutamide). 

Shibukawa et al. (40) discussed the frontal analysis method, also called high-performance frontal analysis (HPFA) or high-performance capillary electrophoresis/frontal analysis (HPCE/FA), compared it to conventional methods, and focused on the application to stereoselective protein binding. The affinity of the drugs warfarin, verapamil, and carbamazepine and the drug candidate BOF-4272 to HSA was investigated. 

There are small changes in serum albumin concentration with age, with concomitant small effects on protein binding of some highly bound drugs such as naproxen, salicylate, and warfarin. For such drugs the free concentration rather than the total plasma concentration is a better predictor of drug dose requirements, particularly for drugs with low therapeutic index (difference between the therapeutic... 

Phenylbutazone was recognised to potentiate the anticoagulant effect of warfarin as long ago as 1959. As subsequent in vitro studies confirmed that phenylbutazone displaced warfarin from its protein binding site, it was assumed that any non-steroidal antiinflammatory drug (NSAID) would enhance warfarin s anticoagulant effect in this way. However it is now known that the interaction is due instead to a stereoselective inhibition of the metabolism of warfarin. Warfarin is available as a racemic mixture of two enantiomers R and S), and of these the S enantiomer is five times more potent as an anticoagulant. Phenylbutazone inhibits the metabolism of the... 

A) An adverse drug reaction may occur if warfarin is displaced from plasma protein binding sites. 

Sulfasalazine can inhibit the absorption of cardiac glycosides and folic acid. It may displace certain drugs, including warfarin, phenytoin, methotrexate, tolbutamide, chlorpropamide, and oral sulfonylureas, from their protein binding sites. Sulfasalazine can diminish the effectiveness of penicillins and estrogen-containing oral contraceptives. 

P] Inhibited warfarin metabolism displaces from protein binding. 

Sulfonamides [NE] Inhibit warfarin metabolism displace protein binding. 

In vitro plasma protein binding of donepezil is 96%, mainly to albumin (75%). Plasma protein binding competition with furosemide, digoxin and warfarin showed that... 

Ultrafiltration has been used to determine the protein bound fraction of many drags, such as methadone (Wilkins et al. 1997), phenylacetate and phenylbu-tyrate (Boudoulas et al. 1996), etoposide (Robieux et al. 1997), doxorubicin and vincristine (Mayer and St-Onge 1995), disopyramide (Echize et al. 1995), and ketamine and its active metabolites (Hijazi and Boulieu 2002). Schumacher et al. (2000) have shown the applicability for the determination of erythro-cyte/plasma distribution. The method of UF has been applied in the measurement of free unaltered thyroxin or after displacement by salicylate as well after displacement by heparin in healthy people and in patients with non-thyroidal somatic illness (Faber et al. 1993). The protein binding of tritium labeled, antidiabetic repaglinide and its displacement by warfarin, furosemide, tolbutamide, diazepam, glibenclamide and nicardipine were determined by ultrafiltration (Plumetal. 2000). 

Pinkerton TC, Koeplinger KA (1990) Determination of warfarin-human serum albumin protein binding parameters by an improved Hummel-Dreyer high performance liquid chromatography method using internal surface reversed-phase columns. Anal Chem 62 2114-2122. 

Protein-binding and Warfarin, other coumarins Reduce dose by 50%,... 

Fibrates should be used cautiously with warfarin and other coumarins, as the INR may rise significantly. The dose of anticoagulant should be reduced by 50% and then adjusted to INR or PT, using serial measurements [1, 28]. This is in addition to the effect of fibrates on haemoglobin, fibrinogen and antithrombin III, and the interaction may be related to displacement of warfarin from protein-binding site [28]. Fatalities have been reported. 

BICALUTAMIDE ANTICOAGULANTS-WARFARIN t plasma concentrations of warfarin Bicalutamide displaces warfarin from protein-binding sites Monitor INR at least weekly until stable at initiation and discontinuation of concurrent therapy... 

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