Why the study?
Does amiodarone alter the pharmacokinetics and tissue uptake of digoxin in rats?
Does amiodarone alter the pharmacokinetics and tissue uptake of digoxin in rats?
Amiodarone significantly increases serum digoxin levels by inhibiting its renal tubular uptake, providing a mechanistic explanation for this critical drug-drug interaction.
May warrant digoxin monitoring with amiodarone coadministration; leaves open human pharmacokinetic confirmation.
Amiodarone is a new antiarrhythmic drug, commonly coadministered with digoxin in various cardiac disorders. Amiodarone caused a 10-fold increase of serum digoxin in rats, when the two drugs were simultaneously administered. Amiodarone significantly reduced digoxin uptake by renal cortical slices in the rat, and failed to reduce digoxin uptake by either heart or diaphragmatic muscle. The inhibition of the renal tubular uptake of digoxin caused by amiodarone may explain in part the increased serum digoxin concentration observed in vivo. Close resemblance was found between the mechanisms involved in the amiodarone-digoxin interaction, and those of digoxin interaction with either quinidine or verapamil.
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Koren et al. (1983) studied this question.
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