DISPOSITION KINETICS OF DIHYDROQUINIDINE FOLLOWING QUINIDINE ADMINISTRATION

  • 1 January 1976
    • journal article
    • research article
    • Vol. 14  (2) , 215-225
Abstract
The disposition kinetics of dihydroquinidine, a known impurity in drug grade quinidine, was studied in 7 patients hospitalized for control of cardiac arrhythmias. Quinidine gluconate injection containing 5.4-6.2% dihydroquinidine was used. Following an overnight fast, dihydroquinidine doses of 0.16-0.31 mg/kg base were infused i.v. over 22 min. Plasma samples were collected at various times for 12 h and analyzed for dihydroquinidine by a TLC-fluorometric assay procedure. Postinfusion plasma dihydroquinidine concentration decline was described by a biexponential equation which suggested that the impurity distributes within the body in 2 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 half-life of the fast (t1/2.alpha.) and slow (t1/2.beta.) disposition processes were 4.71 .+-. 0.26 min and 5.71 .+-. 1.00 h. Total plasma clerance was 4.17 .+-. 0.68 ml/min per kg. Renal excretion of intact dihydroquinidine accounted for 16% of the administered dose. The corresponding value for renal dihydroquinidine clearance (Clr) was 0.61 .+-. 0.08 ml/min per kg. There were apparently no significant differences in the distribution and elimination characteristics of dihydroquinidine and quinidine.