Altered protein binding of quinidine in patients with atrial fibrillation and flutter.

Study Objectives: To determine if alpha1-acid glycoprotein (AAG) concentrations are altered in patients with atrial fibrillation and flutter (AFF), and to establish if fluctuations in AAG change the free fraction of quinidine.
Design: Prospective, controlled, nonrandomized.
Setting: Tertiary care medical center and outpatient clinics.
Patients: Thirty patients with AFF and 16 matched controls.
Interventions: Serial blood samples were collected from patients with AFF at baseline and for 28 days after cardioversion. The control group received no treatment and a single blood sample was obtained.
Measurements and Main Results: Concentrations of AAG were measured by Laurell-Rocket immunoelectrophoresis. Quinidine concentrations were determined by fluorescence polarization immunoassay using the Abbott TDx system. Baseline AAG concentrations in patients with AFF (122 +/- 55 mg/dl) were significantly increased compared with the control group (62 +/- 28 mg/dl, p<0.0005). Concentrations of AAG remained elevated after conversion to sinus rhythm and did not significantly change over the study period, regardless of method of cardioversion (p>0.2). In patients with AFF, the free fraction of quinidine at the highest AAG concentration was 8.5 +/- 2.3%. This was significantly reduced compared with the value in the control group (12.5 +/- 3.0%, p<0.05) as well as that in patients with AFF at the lowest AAG concentration (11.0 +/- 2.5%, p<0.05). Overall at the highest AAG concentration, patients with AFF had a relative reduction in the quinidine free fraction by 32% compared with controls. Regression analysis showed an indirect relationship between serum AAG concentration and the unbound fraction of quinidine (r=0.56)
Conclusions: Concentrations of AAG are increased in patients with AFF and remain elevated for at least 28 days after cardioversion. Elevated AAG concentrations significantly reduce the free fraction of quinidine.