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


METHODS
Prospective, controlled, nonrandomized.


METHODS
Tertiary care medical center and outpatient clinics.


METHODS
Thirty patients with AFF and 16 matched controls.


METHODS
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.


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.
McCollam
P L
PL
Department of Pharmacy Practice, Medical University of South Carolina, Charleston, USA.
Crouch
M A
MA
Watson
J E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000493:pharmacokinetics*; D001281:Atrial Fibrillation / Q000097:blood / Q000378:metabolism*; D004554:Electric Countershock; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009961:Orosomucoid / Q000032:analysis* / Q000378:metabolism; D011446:Prospective Studies; D011485:Protein Binding; D011802:Quinidine / Q000097:blood* / Q000493:pharmacokinetics*; D012044:Regression Analysis; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D009961:Orosomucoid; D011802:Quinidine