OBJECTIVE: The
orosomucoid(ORM) is a major binding protein in plasma for various basic drugs. METHODS: ORM is coded by two
loci closely linked on chromosome. ORM1 locus is high polymorphic and the ORM2 locus is monomorphic in all population. 28 healthy volunteers were selected with three OAN1
phenotypes, containing homozygotes ORM1 F1(n=10) and ORMI S(n=8), and heterozygote ORMI F1S(n=10), identified by isoelectric focusing on polyacrylamide gels following by immunoblotting after desialylation of sera. After a single oral dose of quinidine 200 mg, serum total concentration(HPLC) and unbound concentrations in ultrafiltrate (ultrafiltration/HPLC) were determined, and the pharmacokinetic parameters and
protein binding rate were calculated. Serum levels of ORM(553.8-573.2 mg.L-1) and albumin proteins (57.5-58.4 g.L-1) were similar in the three groups(P>0.05). Unbound quinidine concentration in ORM1 F1 phenotype subjects was higher than that in ORMI S and ORMI FIS phenotype; the free drug percentage for the subjects with ORMI F1 phenotype(19.79%) RESULT: 24 hours after dosing was twice times as high as that with ORMI S phenotype(10.96%) (P<0.01). The elimination t1/2 values and the other pharmacokinetics parameters of quinidine were not affected by the different ORM1 phenotypes. These findings suggested that the different ORM1 phenotypes may affect the disposition of quinidine. The functional heterogeneity of ORM1 could be responsible for the differences in plasma binding of quinidine. CONCLUSION: Therefore, monitoring of the unbound quinidine concentration would be important for the patients with different ORM1 phenotypes when quinidine treatment.