Changes in the binding capacity of alpha-1-acid glycoprotein in patients with renal insufficiency.
The elevation of alpha-1-acid glycoprotein (AAG) concentration and the binding characteristics of disopyramide (DP) to AAG in patients with renal insufficiency were investigated. The serum AAG concentration and protein binding of DP in patients were significantly greater than those in healthy subjects. However, in both the serum and the purified AAG, Scatchard analysis showed that the number of binding sites per molecule of AAG in patients was significantly lower than that in healthy subjects, although there was no difference in the dissociation constant (Kd). These results suggest that the AAG induced in renal insufficiency is qualitatively different from normal AAG. Moreover, the change of the unbound DP fraction when DP concentration was increased was larger in the patients than in the healthy controls. Therefore, monitoring of the unbound DP would be important for therapeutic drug monitoring in patients with renal insufficiency.
Kishino
S
S
Department of Pharmacy, Hokkaido University Hospital, Hokkaido University, Sapporo, Japan.
Nomura
A
A
Di
Z S
ZS
Sugawara
M
M
Iseki
K
K
Kakinoki
S
S
Kitabatake
A
A
Miyazaki
K
K
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004206:Disopyramide / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000378:metabolism*; D011485:Protein Binding; D051437:Renal Insufficiency / Q000097:blood* / Q000188:drug therapy
D001798:Blood Proteins; D009961:Orosomucoid; D003404:Creatinine; D004206:Disopyramide