Hyponatremia Clinical Update, August 23, 2011

Grapefruit juice appears to increase the bioavailability of tolvaptan, a non-peptide arginine vasopressin antagonist, but does not affect its systemic elimination, in healthy subjects, according to the results of a recent study.

The adverse event profile was consistent with the aquaretic effect of tolvaptan as urinary frequency, thirst, and dry mouth were the most frequently reported events, researchers from Otsuka Pharmaceutical Development & Commercialization reported in an abstract for the study, which was published in the European Journal of Clinical Pharmacology.

Tolvaptan is a selective vasopressin V2 receptor antagonist that can be given orally once daily for treatment of clinically significant hypervolemic and euvolemic hyponatremia in the US and Europe or extracellular volume expansion despite taking other diuretics in Japan.

“A single-center, randomized, crossover trial of 60-mg tolvaptan with 240 mL of water or with 240 mL of reconstituted grapefruit juice (washout period of 72 h between doses) was conducted in 20 healthy subjects. Blood samples for tolvaptan plasma concentrations were obtained for 48 h postdose,” the authors wrote in the study abstract.

“All subjects completed the trial. Following co-administration with grapefruit juice, tolvaptan concentrations were elevated compared with tolvaptan alone for only 16 h postdose; consequently, the mean elimination half-life of tolvaptan was unchanged, 5.7 vs 5.1 h respectively. The mean maximal plasma concentration (C(max)) and the area under the curve (AUC(∞)) of tolvaptan were increased 1.86- and 1.56-fold respectively when co-administered with grapefruit juice,” the researchers concluded.

SourcesEffect of Grapefruit Juice on the Pharmacokinetics of Tolvaptan, a Non-peptide Arginine Vasopressin Antagonist, in Healthy Subjects [European Journal of Clinical Pharmacology]