Effect of protein binding of pilsicainide on the pharmacokinetics.
To evaluate the effect of protein binding of pilsicainide on its clearance and the contribution of protein binding to optimized pilsicainide therapy, clinical laboratory and pharmacokinetic data were studied in 160 Japanese inpatients (Study 1) and 18 Japanese inpatients (Study 2). To determine the relation between protein concentration and the protein binding ratio of pilsicainide in vitro, the effect of human alpha1-acid glycoprotein (AAG) and human albumin on the binding ratio was studied. The mean ratio of serum pilsicainide concentration to dose per body weight (C/D) increased with increases in the C-reactive protein (CRP) concentration in Study 1. The AAG level increased with increases in the CRP concentration and the binding ratio increases in the AAG concentration in the Study 2. The binding ratios increased with increased AAG and albumin concentrations; the AAG concentration relative to the ratio was particularly large in vitro study. These results suggest C/D is increased in patients with high CRP levels because of binding of pilsicainide to protein, resulting decreased clearance.
Fukumoto
Kyoko
K
Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Tanemura
Mamiko
M
Tsuchishita
Yoshimasa
Y
Kusumoto
Masaaki
M
Matsumoto
Kana
K
Kamakura
Shiro
S
Ueno
Kazuyuki
K
D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000378:metabolism* / Q000493:pharmacokinetics*; D002097:C-Reactive Protein / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003404:Creatinine / Q000097:blood; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D008875:Middle Aged; D009961:Orosomucoid / Q000032:analysis; D011485:Protein Binding
D000889:Anti-Arrhythmia Agents; D009961:Orosomucoid; D002097:C-Reactive Protein; D008012:Lidocaine; C042288:pilsicainide; D003404:Creatinine