Delayed effect of grapefruit juice on pharmacokinetics and pharmacodynamics of tacrolimus in a living-donor liver transplant recipient.
Tacrolimus is a calcineurin inhibitor that has been widely used to prevent allograft rejection after transplantation. We report a case of a living-donor liver transplant recipient experiencing a considerable increase in the trough blood concentration of tacrolimus after concomitant ingestion of grapefruit juice (250 mL) 4 times for 3 days. The trough blood concentrations of tacrolimus were not changed during or immediate after the repeated intake of grapefruit juice. However, almost 1 week after the final ingestion, the blood concentration of tacrolimus markedly increased to as much as 47.4 ng/mL from 4.7 ng/mL before the ingestion, resulting in a profound reduction of calcineurin phosphatase activity in peripheral blood mononuclear cells. Furthermore, headache and nausea, but not nephrotoxicity or hyperglycemia, took place throughout the period of the elevated blood concentrations. Grapefruit juice may have a clinically significant effect on the pharmacokinetics and pharmacodynamics of tacrolimus. It is recommended to avoid the consumption of grapefruit juice in transplant recipients treated with tacrolimus.
Fukatsu
Sachio
S
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan.
Fukudo
Masahide
M
Masuda
Satohiro
S
Yano
Ikuko
I
Katsura
Toshiya
T
Ogura
Yasuhiro
Y
Oike
Fumitaka
F
Takada
Yasutsugu
Y
Inui
Ken-ichi
K
D000328:Adult; D001499:Bayes Theorem; D001628:Beverages; D032083:Citrus paradisi / Q000737:chemistry*; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D016031:Liver Transplantation / Q000502:physiology*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*
D007166:Immunosuppressive Agents; C120817:calcineurin phosphatase; D010744:Phosphoric Monoester Hydrolases; D016559:Tacrolimus