TROUGH CONCENTRATIONS OF CYCLOSPORINE IN BLOOD FOLLOWING ADMINISTRATION WITH GRAPEFRUIT JUICE

Components of grapefruit juice have been shown to inhibit CYP3A4 activ ity, the enzyme involved in cyclosporine metabolism. Eleven medically stable patients (seven males, four females) receiving cyclosporine fol lowing kidney transplantation were instructed to take their usual dose of cyclosporine with water for 1 week (Phase 1), with grapefruit juic e (8 ounces) for 1 week (Phase 2) and again with water for 1 week (Pha se 3). Trough blood samples were obtained at the end of each phase for measurement of cyclosporine concentration using a specific monoclonal whole blood radioimmunoassay. Cyclosporine trough concentrations aver aged 116.9 +/- 51.6 ng ml-1 in the first phase, 145.3 +/- 44.7 ng ml-1 with grapefruit j uice (P < 0. 05 compared with the first and third p hases) and 111. 2 +/- 56.1 ng ml-1 in the third phase. Cyclosporine co ncentrations increased in 8 of 11 patients when given with grapefruit juice (mean increase 32%; range -4 to 97%) and declined in 10 of 11 wh en subjects resumed taking cyclosporine with water (mean decrease 27%) . These results suggest that grapefruit juice increases trough concent rations of cyclosporine in blood, possibly by inhibiting pre-hepatic g ut wall metabolism, and could be useful in optimizing therapy with thi s drug.