The pharmacokinetics and pharmacodynamics of quinidine and 3-hydroxyquinidine.
1. The pharmacokinetics and pharmacodynamics of quinidine and 3-hydroxyquinidine based upon measurements of total and unbound serum concentrations were determined after a single dose (400 mg) and at steady state (200 mg every 6 h). 2. The oral clearance (7.6 +/- 1.9 vs 4.8 +/- 2.0 ml min-1 kg-1; P less than 0.05) and renal clearance (1.2 +/- 0.3 vs 0.63 +/- 0.25 ml min-1 kg-1; P less than 0.005) or quinidine were lower during steady state than after the single dose. 3. The area under the serum concentration vs time curve (AUC) of 3-hydroxyquinidine was greater at steady state than after the single dose (2.0 +/- 0.7 vs 3.0 +/- 0.6 mg l-1 h; P less than 0.05) and its renal clearance was less (3.0 +/- 1.1 vs 1.54 +/- 0.38 ml min-1 kg-1; P less than 0.05). 4. The slope of the relationship between quinidine concentration and change in QTc interval was greater at steady state (40.1 +/- 21.7 vs 72.2 +/- 41.7 ms/(mg l-1); P less than 0.05).
Wooding-Scott
R A
RA
Department of Pharmacy, State University of New York, Buffalo 14260.
Smalley
J
J
Visco
J
J
Slaughter
R L
RL
D000328:Adult; D004562:Electrocardiography; D006801:Humans; D008297:Male; D011485:Protein Binding; D011802:Quinidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology
C013569:3-hydroxyquinidine; D011802:Quinidine