Altered drug-serum protein binding in the genetically obese Zucker rat

J Pharm Sci. 1985 Aug;74(8):837-40. doi: 10.1002/jps.2600740807.


Drug-serum protein binding was evaluated in genetically obese Zucker rats, their lean littermates, and lean Sprague-Dawley rats. The free fraction (fp) of phenytoin was significantly higher in the obese rat (fp = 0.177) compared to its lean littermate (fp = 0.136), apparently due to displacement by free fatty acids. Conversely, diazepam and propranolol fp values were decreased in the obese Zucker rat (fp = 0.107 and fp = 0.122, respectively) compared to the lean Zucker rat (fp = 0.140 and fp = 0.174, respectively). Evidence strongly suggests that the increased binding of propranolol was not due to elevations in the serum concentrations of alpha1-acid glycoprotein (as is the case in the human obese population). Rather, the decreased fp for both diazepam and propranolol was a result of increased lipoprotein partitioning. Strain differences between the lean Zucker rat and lean Sprague-Dawley rat were also evident, with serum binding of the Sprague-Dawley rat more closely resembling the obese Zucker rat.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Blood Proteins / metabolism*
  • Diazepam / blood
  • Female
  • Models, Biological
  • Organophosphorus Compounds
  • Pharmaceutical Preparations / blood*
  • Phenytoin / blood
  • Propranolol / blood
  • Protein Binding
  • Rats
  • Rats, Inbred Strains
  • Rats, Zucker
  • Species Specificity


  • Blood Proteins
  • Organophosphorus Compounds
  • Pharmaceutical Preparations
  • Phenytoin
  • Propranolol
  • Diazepam
  • tris(2-butoxyethyl) phosphate