QUINIDINE SULFATE- quinidine sulfate tablet, film coated, extended release
QUINIDINE GLUCONATE- quinidine gluconate solution
Eli Lilly and Company
Teva Pharmaceuticals USA Inc
DESCRIPTION
Quinidine is an antimalarial schizonticide and an antiarrhythmic agent with Class Ia activity; it is the d-isomer of quinine, and its molecular weight is 324.43. Quinidine sulfate is the sulfate salt of quinidine; its chemical name is cinchonan-9-ol, 6�-methoxy-, ( 9S)-, sulfate (2:1) (salt) dihydrate; its molecular weight is 782.94, of which 82.9% is quinidine base
Each Quinidine Sulfate Extended-release Tablet contains 300 mg of quinidine sulfate (249 mg of quinidine base) in a formulation to provide extended release; the inactive ingredients are: fumaric acid, hypromellose, lactose monohydrate, magnesium stearate, polydextrose, polyethylene glycol, povidone, triacetin and titanium dioxide.
These tablets comply with USP Drug Release Test 1.
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY
Pharmacokinetics and Metabolism � After intramuscular injection of quinidine gluconate, peak serum levels of quinidine are achieved in a little less than two hours. This time to peak levels is identical to the time measured when quinidine salts are administered orally.
Pharmacokinetics
The absolute bioavailability of quinidine from quinidine sulfate is about 70%, but this varies widely (45-100%) between patients. The less-than-complete bioavailability is the result of first-pass metabolism in the liver. Peak serum levels generally appear about 6 hours after dosing. Although the effect of food upon quinidine sulfate absorption has not been studied, peak serum quinidine levels obtained from immediate-release quinidine sulfate are known to be delayed by nearly an hour (without change in total absorption) when these products are taken with food. The volume of distribution of quinidine is 2 to 3 L/kg in healthy young adults, but this may be reduced to as little as 0.5 L/kg in patients with congestive heart failure, or increased to 3 to 5 L/kg in patients with cirrhosis of the liver. At concentrations of 2 to 5 mg/L (6.5 to 16.2 ?mol/L), the fraction of quinidine bound to plasma proteins (mainly to ?1 -acid glycoprotein and to albumin) is 80 to 88% in adults and older pediatric patients, but it is lower in pregnant women, and in infants and neonates it may be as low as 50 to 70%. Because ?1- acid glycoprotein levels are increased in response to stress, serum levels of total quinidine may be greatly increased in settings such as acute myocardial infarction, even though the serum content of unbound (active) drug may remain normal. Protein binding is also increased in chronic renal failure, but binding abruptly descends toward or below normal when heparin is administered for hemodialysis.
