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  • Title: Displacement of thiopental from human serum albumin by associated drugs.
    Author: Russo H, Audran M, Bressolle F, Brès J, Maillols H.
    Journal: J Pharm Sci; 1993 May; 82(5):493-7. PubMed ID: 8360825.
    Abstract:
    Displacement of thiopental from its binding sites to 4% human serum albumin solution was studied in vitro. Experimental conditions were selected to reproduce a physiological situation. Associations were studied according to the therapeutic conditions of use of the substances (drug and protein concentrations). The unbound fraction of thiopental was obtained by equilibrium dialysis at 37 degrees C and pH 7.4. Eleven drugs were associated with thiopental in 50 combinations of drugs and molar ratios. Bromhexine, citocoline, dextromoramide, dexamethasone, and methotrimeprazine had no effect on thiopental binding. The unbound fraction of thiopental significantly increased with cefamandole, cefazolin, diazepam, desmethyldiazepam, furosemide, and fentanyl. At usual therapeutic drug concentrations, the unbound fraction increase was < 5%. Higher values, however still < 10%, were found with associated drugs that were added at maximal concentrations observed in therapy. The displacement of thiopental from its albumin binding by drugs that are normally associated with the treatment of intracranial hypertension does not modify the pharmacokinetic parameters or pharmacological effect of thiopental.
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