ALTERED PROTEIN-BINDING OF QUINIDINE IN PATIENTS WITH ATRIAL-FIBRILLATION AND FLUTTER

Study Objectives. To determine if al-acid glycoprotein (FLAG) concentr ations are altered in patients with atrial fibrillation and flutter (A FF), 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 bloo d 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. Co ncentrations of AAG were measured by Laurell-Rocket immunoelectrophore sis. Quinidine concentrations were determined by fluorescence polariza tion immunoassay using the Abbott TDx system. Baseline AAG concentrati ons in patients with AFF (122 +/- 55 mg/dl) were significantly increas ed compared with the control group (62 +/- 28 mg/dl, p < 0.0005). Conc entrations of AAG remained elevated after conversion to sinus rhythm a nd did not significantly change over the study period, regardless of m ethod of cardioversion (p > 0.2). In patients with AFF; the free fract ion of quinidine at the highest AAG concentration was 8.5 +/- 2.3%. Th is was significantly reduced compared with the value in the control gr oup (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. Regress ion analysis showed an indirect relationship between serum AAG concent ration and the unbound fraction of quinidine (r = 0.56). Conclusions. Concentrations of AAG are increased in patients with AFF and remain el evated for at least 28 days after cardioversion. Elevated AAG concentr ations significantly reduce the free fraction of quinidine.