Adverse effect

Dosing

Pharmacokinetics

Trough Concentration

Bioavailability

Grapefruit juice

Internal medicine

Pharmacology

Medicine

Dose

Internal Medicine

Objective It is well known that grapefruit juice (GFJ) elevates the blood tacrolimus (TAC) concentration. We investigated the efficacy and safety of GFJ intake with TAC in cases of connective tissue diseases in which the TAC blood concentration was insufficiently high for clinical improvement, even when 3 mg/day or more of TAC was administered. Methods Seven patients took 200 mL of GFJ every day. The trough levels of the TAC blood concentration were measured before and after GFJ intake and the clinical courses were monitored thereafter. Results First, we surveyed the blood TAC trough levels of 30 recent patients who took 3 mg/day of TAC, and found that 21 patients (70%) did not achieve the minimum target TAC concentration (>5 ng/mL). Seven patients took GFJ due to a lack of efficacy and a relatively low TAC blood concentration. GFJ increased the TAC level from 4.3±2.4 ng/mL to 13.8±6.9 ng/mL (average increase: 3.3-fold). GFJ was also effective in achieving a clinical improvement in most cases without causing any severe adverse events, and it helped to decrease the dosages of glucocorticoid and TAC. In some cases, the blood TAC concentration fluctuated for no apparent reason. Conclusion GFJ intake was effective for the elevation of TAC concentration by approximately three fold and clinical improvement, but special care is required for monitoring its influence on concomitantly used drugs as well as TAC concentration. The addition of GFJ to TAC treatment could be an efficacious treatment option, when the plasma TAC concentration does not reach the minimal target concentration.

Efficacy and Safety of Grapefruit Juice Intake Accompanying Tacrolimus Treatment in Connective Tissue Disease Patients