Alteration in plasma protein binding properties of propranolol and flurbiprofen during development of adjuvant-induced arthritis in rats

Xenobiotica. 2013 Mar;43(3):246-52. doi: 10.3109/00498254.2012.710350. Epub 2012 Aug 7.

Abstract

Adjuvant-induced arthritis (AA) in the rat is used as a model for rheumatoid arthritis. In AA rats, the pharmacokinetics of various drugs is affected due to the alterations of plasma protein binding of drugs. We choose propranolol (PL) and flurbiprofen (FP) as model basic and acidic drugs, respectively, and investigated the effect of AA induction on their plasma protein binding at each developing stage of inflammation. The plasma protein binding of PL and FP was dramatically changed due to reduced albumin and increased α₁-acid glycoprotein levels for at least 21 days after adjuvant treatment. Moreover, we illustrated the differences in protein binding in AA between both the drugs in each developing stage of inflammation. These results suggest that the changed plasma protein levels in AA rats accompanying the altered protein binding of drugs affect the pharmacokinetics of drugs which extensively bind to plasma protein under inflammatory condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / blood
  • Animals
  • Arthritis, Experimental / blood*
  • Arthritis, Experimental / pathology*
  • Aspartate Aminotransferases / blood
  • Blood Proteins / metabolism*
  • Female
  • Flurbiprofen / blood
  • Flurbiprofen / metabolism*
  • L-Lactate Dehydrogenase / blood
  • Orosomucoid / metabolism
  • Propranolol / blood
  • Propranolol / metabolism*
  • Protein Binding
  • Rats
  • Rats, Sprague-Dawley
  • Serum Albumin / metabolism

Substances

  • Blood Proteins
  • Orosomucoid
  • Serum Albumin
  • Flurbiprofen
  • Propranolol
  • L-Lactate Dehydrogenase
  • Aspartate Aminotransferases
  • Alkaline Phosphatase