Heparin protein binding

LMWH have higher bioavailability after subcutaneous injection than standard, heparin. LMWH binds less than heparin to plasma proteins. The clearance of LMWH is mainly renal, independent of dose and slower than metabolic clearance of heparin. 

Many proteins bind to motifs in DS, heparin, and HS chains that feature IdoA residues [2, 52], Unfortunately, L-idose and IdoA are very expensive sugars, prompting chemists who wish to target IdoA-containing sequences to use cheaper alternatives for building block preparation [53], Abundant D-glucose-based compounds are often... 

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). 

Affi-Gel Heparin Heparin DNA-binding proteins, BIORAD... 

The use of vacutainer tubes and heparin was shown to alter the determination of protein binding. Heparin was shown to decrease the plasma binding of certain drugs including phenytoin, propranolol, lidocaine, diazepam, quinidine, and verapamil. This is also an in vitro artifact attributable to continued ex vivo activity of the lipoprotein lipase enzyme and accumulation of fatty acids in the blood collection tube. 

An interaction of heparin with digitoxin has been described and ascribed to altered protein binding, secondary to changes in fatty acid concentrations, but the clinical relevance, for example in patients undergoing hemodialysis, is unclear (207). 

Reduced plasma protein binding of digitoxin has been reported after the administration of heparin (111). In 10 hemodialysed patients taking maintenance digitoxin therapy, there was reduced binding in vitro because of heparin-induced lipolysis, and not as a consequence of in vivo binding of digitoxin to plasma proteins. 

Artefactual increases of as much as 50% in total thyroxine, estimated by a competitive protein-binding assay, and of as much as 30% in triiodothyronine resin uptake are probably due to rapid and continuing lipolytic hydrolysis of triglycerides after blood has been drawn (126). Thyroid function tests should therefore always be performed on blood samples taken before (or a sufficient time after) heparin treatment (127). An increase in serum-free thyroxine concentrations has also been reported after low molecular weight heparin, by up to 171% in specimens taken 2-6 hours after injection. When specimens were obtained 10 hours after injection, the effects were smaller, but with concentrations still up to 40% above normal the results can still cause errors of interpretation (128). 

Lohman JJ, Hooymans PM, Koten ML, Verhey MT, Merkus FW. Effect of heparin on digitoxin protein binding. Clin Pharmacol Ther 1985 37(l) 55-60. 

Walters MI, Roberts WH. Gentamicin/heparin interactions effects on two immunoassays and on protein binding. Ther Drug Monit 1984 6(2) 199-202. 

Figure 4-13 A pentasaccharide segment of heparin which binds with high affinity to the serum protein antithrombin causing it to inhibit most of the serine protease enzymes participating in the blood coagulation process (see Chapter 12). See Lindahl et al. ...

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

Fasting plasma (heparin) is the preferred specimen type. In newborns and infants blood should be collected immediately before the next scheduled feeding. Serum is generally derived from blood left to clot at room temperature, a process that leads to artifacts from deamination, loss of sulfiir-containing amino acids due to protein binding, con-... 

Thrombin and factor Xa that have escaped into the blood flow are both inhibited by serpins, anti-thrombin III (ATIII) and heparin cofactor II (HCII). These proteins bind to heparin sulfate or dermatan sulfate (Sect. 6.3.1), glycosaminoglycans which are secreted onto the luminal surface of healthy endothelial cells and also released into the blood from mast cells activated by an injury. Among the heparin molecules is a pentaglycan sequence... 

Fig. 5. Hidden protein-binding sequences in HS. (o) Two different proteins bind to the same, fully sulfated ( regular ) heparin sequence. (Z>) The same proteins interact specifically each with one distinct HS sequence. The symbols are the same as in Fig. 1. For further information see the text.

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