Disposition kinetics of dihydroquinidine following quinidine administration

Abstract

The disposition kinetics of dihydroquinidine, a known impurity in drug grade quinidine, was studied in 7 patients who were hospitalized for control of cardiac arrhythmias. Quinidine gluconate injection containing 5.4 to 6.2 percent dihydroquinidine was used. Following an overnite fast, dihydroquinidine doses of 0.16 to 0.31 mg/kg base were infused intravenously over 22 min. Plasma samples were collected at various times for 12 hr and analyzed for dihydroquinidine by a thin layer chromatography-fluorometric assay procedure. Postinfusion plasma dihydroquinidine concentration decline was described by a biexponential equation which suggested that the impurity distributes within the body in two kinetically distinguishable pools. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.67 +/- 0.15 L/kg and 2.76 +/- 0.63 L/kg, respectively. The halflife of the fast (t1/2alpha) and slow (t1/2beta) disposition processes were 4.71 +/- 0.26 min and 5.71 +/- 1.00 hr. Total plasma clearance was 4.17 +/- 0.68 ml/min/kg. Renal excretion of intact dihydroquinidine accounted for 16 percent of the administered dose. The corresponding value for renal dihydroquinidine clearance (Clr) was 0.61 +/- 0.08 ml/min/kg. The results of this study indicated that there were no significant differences in the distribution and elimination characteristics of dihydroquinidine and quinidine.