Effect of quinine on digoxin kinetics

Area of Science:

• Pharmacology
• Drug Interactions
• Clinical Pharmacology

Background:

• Digoxin is a cardiac glycoside with a narrow therapeutic index.
• Quinidine is known to affect digoxin pharmacokinetics.
• The effects of quinine, an isomer of quinidine, on digoxin pharmacokinetics require elucidation.

Purpose of the Study:

• To evaluate the impact of quinine administration on the pharmacokinetics of digoxin.
• To determine if quinine alters digoxin total body clearance, elimination half-life, and excretion pathways.

Main Methods:

• Six subjects received a 1.0-mg intravenous digoxin dose before and during quinine administration.
• Digoxin serum and urine concentrations were measured for 96 hours post-dose.
• Pharmacokinetic parameters including total body clearance, elimination half-life, and renal/nonrenal clearance were calculated.

Main Results:

• Quinine reduced digoxin total body clearance by 26% (p < 0.03) and increased elimination half-life by 32% (p < 0.003).
• Digoxin renal clearance and volume of distribution were not significantly affected.
• Nonrenal clearance decreased by 55% (p < 0.05), and urinary digoxin excretion increased (p < 0.02).

Conclusions:

• Quinine administration alters digoxin pharmacokinetics, primarily by reducing nonrenal clearance.
• These findings suggest quinine affects digoxin metabolism or biliary secretion.
• The mechanism is qualitatively similar but quantitatively different from that of quinidine.