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Altered plasma drug binding in cancer: Role of α 1 ‐acid glycoprotein and albumin
Author(s) -
Jackson Peter R,
Tucker Geoffrey T,
Woods Hubert F
Publication year - 1982
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 - 10.1038/clpt.1982.163
Subject(s) - albumin , orosomucoid , drug , plasma protein binding , glycoprotein , blood proteins , pharmacology , serum albumin , chemistry , cancer drugs , medicine , biochemistry
Altered concentrations of serum proteins often accompany malignant disease. The effect of these changes on drug binding was studied with lidocaine, a basic drug, and tolbutamide, an acidic drug. Patients with cancer had increased serum concentrations of the acute‐phase protein α 1 ‐acid glycoprotein (AAG) and lowered serum concentration of albumin. In association with these changes lidocaine binding was increased at all concentrations studied (predialysis concentrations 2, 6, and 10 μg · ml −1 ) and that of tolbutamide was decreased at the highest concentration (200 μg · ml −1 ). Not all of the increase in lidocaine binding was explicable on the basis of increased serum AAG concentration. Estimation of binding parameters with a model with two independent sites showed increased affinity at the high affinity site in cancer patients with no change in the calculated number of binding sites. Therefore, in cancer there is increased lidocaine binding in association with increased AAG concentrations. We also record the novel observation of a change in the intrinsic properties of the high affinity binding site. Clinical Pharmacology and Therapeutics (1982) 32, 295–302; doi: 10.1038/clpt.1982.163