Characterization of dexamethasone binding in normal and uremic human serum
| Autor: | Mario L. Rocci, Ghassem E. Larijani, Roger K. Ferguson, Doyle M. Cummings, Dale P. Conner |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Adult
Male medicine.medical_specialty Globulin medicine.medical_treatment Population Serum albumin 030226 pharmacology & pharmacy Dexamethasone Steroid 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine medicine Humans Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics education Serum Albumin Uremia education.field_of_study biology Chemistry Albumin Kinetics Endocrinology Free fraction 030220 oncology & carcinogenesis biology.protein medicine.drug Protein Binding |
| Zdroj: | DICP : the annals of pharmacotherapy. 24(3) |
| ISSN: | 1042-9611 |
| Popis: | The purpose of this study was to examine the extent and linearity of dexamethasone binding over a wide concentration range in normal and uremic serum. Tritiated dexamethasone was added to both untreated and charcoal-treated pooled normal serum and to pooled uremic serum to produce concentrations similar to those attained therapeutically (10-1000 ng/mL). Protein binding was determined by equilibrium dialysis at 37 degrees C. Dexamethasone serum binding was linear over the entire range of concentrations for each set of pooled serum. The mean (+/- SD) percent bound (mean +/- SD) for dexamethasone was similar for untreated (75.1 +/- 3.6 percent) and charcoal-treated (77.3 +/- 3.5 percent) normal serum. Dexamethasone binding (69.2 +/- 1.8 percent, p less than 0.05) and serum albumin concentrations (39.9 vs. 55.1 mmol/L) were significantly less in uremic vs. normal serum, respectively. These results suggest that (1) the binding of dexamethasone is linear and occurs primarily to albumin, with little or no binding to corticosteroid-binding globulin; (2) endogenous cortisol does not compete with dexamethasone for protein binding sites; and (3) steroid pharmacokinetics may be altered in uremic patients due to the 24 percent higher free fraction of dexamethasone in this population. |
| Databáze: | OpenAIRE |
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