title: Alteration in plasma protein binding properties of propranolol and flurbiprofen during development of adjuvant-induced arthritis in rats.
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.
authors.affiliation: Department of Pharmacy, School of Pharmacy, Kinki University, 3-4-1 Kowakae, Higashi-osaka, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kawase
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ikuta
authors.forename: Satoshi
authors.initials: S
authors.lastname: Uno
authors.forename: Kana
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Naomi
authors.initials: N
authors.lastname: Akitsu
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Nagao
authors.forename: Masahiro
authors.initials: M
authors.lastname: Iwaki
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001169:Arthritis, Experimental / Q000097:blood* / Q000473:pathology*; D001219:Aspartate Aminotransferases / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D005260:Female; D005480:Flurbiprofen / Q000097:blood / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D009961:Orosomucoid / Q000378:metabolism; D011433:Propranolol / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D009961:Orosomucoid; D012709:Serum Albumin; D005480:Flurbiprofen; D011433:Propranolol; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000469:Alkaline Phosphatase