Co-administration of grapefruit juice increases bioavailability of tacrolimus in liver transplant patients: a prospective study.

Purpose: The interactions between grapefruit juice (GFJ) and tacrolimus (FK506) metabolism remain obscure. The aim of this prospective study was to explore the effect of GFJ on the blood concentration of FK506 in liver transplant patients.

Methods: Thirty liver transplant patients were enrolled in the study 1 month post-transplant and randomly divided into three equal-sized groups. Group A patients were treated with the standard FK506-based immunosuppressant regimen only and therefore served as the control; group B and C patients were treated with the standard FK506-based immunosuppressant regimen as well as one of two different kinds of GFJ, respectively. The blood concentrations of FK506 on the seventh day after GFJ intake were compared within each group and among groups. The dose of FK506 was adjusted depending on the valley concentration measured to a treatment window.

Results: The blood concentration of FK506 in both group B and group C patients was significantly enhanced, by 1.56 +/- 0.95 and 10.33 +/- 5.59 ng/ml, respectively, following the administration of GFJ for 1 week (compared with the concentration at the start of the experiment in each group; p < 0.05). However, at the end time point, the blood concentration of FK506 in group C patients was significantly increased (p < 0.05) relative to that of the control patients, while this was not the case in group B patients (p > 0.05). Group C patients could be treated with a smaller dose of FK506 (decreased by 2.3 +/- 1.3 mg/day for all patients; p = 0.011), amounting to a decrease in drug costs of approximately $8.70 +/- 5.60/day (p = 0.011).

Conclusion: In the setting of a controlled clinical study, the co-administration of GFJ with FK506 increased the bioavailability of FK506. However, the concentration of tacrolimus should be closely monitored and the dose adjusted to the treatment window.