Summary
The possible development of a displacement interaction involving tolbutamide, in epileptic patients, has been explored by studying the serum protein binding of this drug in vitro in 199 samples of sera from patients treated with antiepileptic agents included in a programme of therapeutic drug monitoring. 82 of the samples were from patients receiving a single drug, 86 from patients treated with 2 drugs, and 31 from patients treated with 3 drugs. The free fraction of tolbutamide was higher in serum from patients treated with antiepileptic drugs than in serum from untreated ‘normal’ volunteers. The increase was more marked the greater the number of antiepileptic drugs administered. Valproate appeared to be the most powerful displacing agent.
Similar content being viewed by others
References
Balant, L.: Clinical pharmacokinetics of sulphonylurea hypoglycaemic drugs. Clinical Pharmacokinetics 6: 215–241 (1981).
Browne, T.R.: Clonazepam: A review of a new anticonvulsant drug. Archives of Neurology 33: 326–332 (1976).
Dhillon, S. and Richens, A.: Serum protein binding of diazepam and its displacement by valproic acid in vitro. British Journal of Clinical Pharmacology 12: 591–592 (1981).
Ehrnebo, M.; Agurell, S.; Jailing, B. and Boréus, L.O.: Age differences in drug binding by plasma proteins: Studies on human foetuses, neonates and adults. European Journal of Clinical Pharmacology 3: 189–193 (1971).
Kober, A.; Olsson, Y. and Sjöholm, I.: Binding of drugs to human serum albumin. XIV. The theoretical basis for the interaction between Phenytoin and valproate. Molecular Pharmacology 18: 237–242 (1980).
Levy, G.: Effect of plasma protein binding of drugs on duration and intensity of pharmacological activity. Journal of Pharmaceutical Sciences 65: 1264–1265 (1976).
Levy, R.H. and Koch, K.M.: Drug interactions with valproic acid. Drugs 24: 543–556 (1982).
MacKichan, J.J. and Zola, E.M.: Carbamazepine binding to plasma, albumin and alpha,-acid glycoprotein. Clinical Pharmacology and Therapeutics 31: 246 (1982).
McElnay, J.C. and D’Arcy, P.F.: Protein binding displacement interactions and their clinical significance. Drugs 25: 495–513 (1983).
Müller, W. and Wollen, U.: Characterization of the binding of benzodiazepines to human serum albumin. Naunyn-Schmie-deberg’s Archives of Pharmacology 280: 229–237 (1973).
Prescott, L.F. and Redman, D.R.: Gas-liquid chromatographic estimation of tolbutamide and chlorpropamide in plasma. Journal of Pharmacy and Pharmacology 24: 713–716 (1972).
Sellers, E.M.: Plasma protein displacement interactions are rarely of clinical signficance. Pharmacology 18: 225–227 (1979).
Sjöholm, I.; Ekman, B.; Kober, A.; Ljungstedt-Pahlman, I.; Seiving, B. and Sjödin, T.: Binding of drugs to human serum albumin. XI. The specificity of three binding sites as studied with albumin immobilized in microparticles. Molecular Pharmacology 16: 767–777 (1979).
Williams, R.L.; Blaschke, T.F.; Meffin, P.J.; Melmon, K.L. and Rowland, M.: Influence of acute viral hepatitis on disposition and plasma binding of tolbutamide. Clinical Pharmacology and Therapeutics 21: 301–309 (1977).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Fernández, M.C., Erill, S., Lucena, M.I. et al. Serum Protein Binding of Tolbutamide in Patients Treated with Antiepileptic Drugs. Clin Pharmacokinet 10, 451–455 (1985). https://doi.org/10.2165/00003088-198510050-00007
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-198510050-00007