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Clinical pharmacology of the new penicillins: II. Effect of drugs which interfere with binding to serum proteins
Author(s) -
Kunin Calvin M.
Publication year - 1966
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt196672180
Subject(s) - dicloxacillin , nafcillin , cloxacillin , penicillin , chemistry , pharmacology , antibiotics , probenecid , in vivo , drug , medicine , biochemistry , microbiology and biotechnology , biology
A series of compounds were found to be effective in vitro inhibitors of serum protein binding of penicillins G, V, ancillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin when used at a molar concentration of 1 x 10 −3 versus the penicillins at 1 x 10 −4 M. Three of these compounds, sulfamethoxypyridazine, sulfaethylthiadiazole, and acetylsalicylic acid were employed in volunteer studies to determine their effect on serum concentrations and binding of the various penicillin analogues in vivo. it was possible to reduce serum binding of the penicillins in man by this approach with all of the penicillin analogues studied, including the very highly bound drug, dicloxacillin. When effective, binding inhibitors tended to lower concentrations in serum of total penicillin and in almost all instances significantly increased the concentrations of unbound antibiotic. Sulfonamides interfered with the oral absorption of oxacillin. The limitations of this approach to current therapy with penicillins are presented together with a brief description of the features of a desirable new penicillin analogue.