Effect of quinine on digoxin kinetics

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Abstract
Six subjects were evaluated for the effect of quinine, the l-quinidine, on digoxin pharmacokinetics. A 1.0/mg i.v. digoxin dose was given before and during quinine administration, followed by the measurement of digoxin serum and urine concentrations for 96 h after each dose. Quinine reduced digoxin total body clearance by 26% from 2.98 to 2.22 ml/min per kg (P < 0.03). Digoxin elimination half-life (t1/2) was lengthened from 34.2-51.8 h, reflecting a 32% decrease in digoxin elimination rate constant (P < 0.003). Quinine did not reduce digoxin renal clearance or any volumes of distribution. The amount of digoxin excreted into the urine increased from .hivin.x [mean] = 628.29-772.52 .mu.g (P < 0.02). Digoxin nonrenal clearance decreased an average of 55% from 1.2-0.55 ml/min per kg (P < 0.05). Quinine alters digoxin metabolism or biliary secretion, reducing digoxin total body clearance by a mechanism that is qualitatively similar, but quantitatively different, from quinidine.