Influence of the ORM1 phenotypes on serum unbound concentration and protein binding of quinidine.
作者： Jin-Heng Li , Jing-Qiu Xu , Xiao-Mei Cao , Li Ni , Yong Li
DOI: 10.1016/S0009-8981(01)00763-X
关键词: Biology 、 Blood proteins 、 Endocrinology 、 Population 、 Plasma protein binding 、 Albumin 、 Isoelectric focusing 、 Orosomucoid 、 Pharmacology 、 Internal medicine 、 Binding protein 、 Pharmacokinetics
摘要: Abstract Background: Only unbound or free drug in plasma can be transported to its site of action. The fraction varies widely for highly bound drugs among individuals. genetic polymorphism orosomucoid (ORM) could related the interindividual variability binding basic drugs, as ORM is transport protein these plasma. a major various and coded by two loci, ORM1 ORM2, which are closely linked on chromosome 9q31→34.1. locus polymorphic ORM2 monomorphic most population. Methods: Twenty-eight healthy volunteers were selected with three phenotypes, containing homozygotes F1 (n=10) S (n=8), heterozygote F1S (n=10), identified isoelectric focusing polyacrylamide gels followed immunoblotting after desialylation sera. After single oral dose quinidine 200 mg, serum total (HPLC) concentrations ultrafiltrate (ultrafiltration/HPLC) determined, pharmacokinetic parameters rate calculated. Results: Serum (553.8–573.2 mg/l) albumin proteins (57.5–58.4 similar groups (P>0.05). Unbound concentration phenotype subjects was higher than that phenotype; percentage (19.79%) twice high (10.96%) (P
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