Unusual Pharmacokinetic Herb-Drug Interactions between Turmeric Crude Extract and Digoxin in Male Volunteers

Abstract

Curcuminoids, the major components of Curcuma longa L. (turmeric), have inhibitory properties against P-glycoprotein, an efflux transporter found in the intestine. It is reasonable to hypothesize that the inhibition of P-glycoprotein-mediated transport by curcuminoids can cause an increase in plasma concentrations of P-glycoprotein substrates, such as digoxin, in the human body. In our previous randomized crossover study, we observed an increase in digoxin plasma concentrations following concomitant use of a turmeric crude extract equivalent to 1,000 mg of curcuminoids per day in a majority of healthy male volunteers. However, there were two volunteers whose pharmacokinetic changes were opposite to those of the other volunteers; that is, digoxin plasma concentrations were markedly decreased after the concomitant use of the turmeric crude extract. In the present article, we report the results of our repeated experiment with these two volunteers using a different digoxin formulation (i.e., digoxin elixir). With digoxin elixir, the unusual pharmacokinetic pattern was somewhat similar to that observed in the corresponding experiment with digoxin tablets. The consistent results between initial and repeated experiments ensured that the unusual pharmacokinetic herb-drug interaction was not mainly attributable to an abnormal disintegration or dissolution of the digoxin tablets. Precaution should be taken when the turmeric crude extract is concurrently taken with P-glycoprotein substrates. Not only an increase in plasma concentrations of P-glycoprotein substrates, but also a decrease in plasma concentrations of such substrates could occur.