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The pharmacokinetics and pharmacodynamics of quinidine and 3‐ hydroxyquinidine.
Author(s) -
WoodingScott RA,
Smalley J,
Visco J,
Slaughter RL
Publication year - 1988
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1988.tb03400.x
Subject(s) - quinidine , pharmacokinetics , steady state (chemistry) , pharmacodynamics , pharmacology , chemistry , area under the curve , medicine
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).