Pharmacokinetics of quinidine related to plasma protein binding in man

The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134--0.303 (mean 0.221). Elimination rate constant (beta) varied from 0.071 to 0.146 h-1 (mean 0.113), and apparent volume of distribution (Vbeta) varied from 1.39--3.20 1 . kg-1 beta (mean 2.27). Total body clearance was 2.32--6.49 ml min-1 . kg-1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both V beta (r = 0.885, p less than 0.01) and total body clearance (r = 0.668, p less than 0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compound and its elimination rate will remain unaffected.