Heparin-Antibiotic Interactions

Background to Method and Results of Conductivity Titrations of Heparin against Aminoglycoside and Penicillin Antibiotics 

Certain aminoglycoside antibiotics, including gentamicin and streptomycin, have been observed to interact with the acidic mucopolysaccharide heparin, condroitin sulfate, and hylauronic acid with reduction of antibacterial activity. The interaction of aminoglycosides with the acidic mucopolysaccharides has been suggested to result in the accumulation of the drug in the kidney and in the inner ear and to partly account for the well-documented nephrotoxicity and ototoxicity of this group of antibiotics. 

In view of the above observations it seems appropriate to follow the reaction between heparin and antibiotics by conductometric titration, using the usual method. 0.5 x 10 molar solutions of antibiotic were used because these are well-characterized chemical entities and the concentrations are reasonably close to the practical therapeutic range. Heparin, however, is not well characterized and its concentrations are usually indicated in terms of a unit of activity which is defined in terms of 

The results suggest a positive interaction between heparin and the aminoglycoside antibiotics. There appears to be no interaction between heparin and penicillin or cloxacillin within the precision of the measurement, a perfect straight line results, linking the conductance of the two components. 

In these carriers, the antibiotic is quite firmly held in higher aggregates, and not likely to be available for any bactericidal action thus, complexation with heparin should considerably lower biological activity, as confirmed in microbiology tests. 

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Heparin has been reported to complex with a variety of basic species, including biogenic amines and drugs for reviews, see Refs. 10 and 391. For its possible relevance to the pharmacological properties of heparin and complexed species, mention is made here of complexes with histamine392,393 and anthracycline antibiotics.394 C.d. studies on the interaction of basic homopolypeptides with heparin and other glycosaminogly-cans have shown that heparin is able to induce an ordered, helical conformation in the polypeptide.395 397 Similar, and even more dramatic, effects were observed with mixed basic polypeptides, presumed to represent better models for the biologically relevant interactions with plasma proteins.368... 

Examples will now be considered of the application of electrochemical techniques to the interactions of chlorpromazine and other phenothiazine derivatives, heparin, and antibiotics. 

Electrochemistry of Drug Interactions and Incompatibilities 6, Interactions between Heparin and Antibiotics... 

The possible interaction between heparin and the cationic aminoglycoside antibiotics would appear suitable for investigation by electrochemical methods. 

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