L. Backman et al., FK506 THROUGH LEVELS IN WHOLE-BLOOD AND PLASMA IN LIVER-TRANSPLANT RECIPIENTS - CORRELATION WITH CLINICAL EVENTS AND SIDE-EFFECTS, Transplantation, 57(4), 1994, pp. 519-525
FK506 trough levels were measured by ELISA in paired whole-blood and p
lasma samples in 59 liver transplant recipients. Patients with nephrot
oxicity had higher FK506 whole-blood and plasma levels (27.5+/-3.2 ng/
ml and 1.44+/-0.14 ng/ml) than patients with stable liver function (15
.2+/-2.1 ng/ml and 0.98+/-0.15 ng/ml, P<0.05 and P<0.01, respectively)
. Patients with acute rejection had FK506 whole-blood and plasma level
s within the same range as patients with stable liver function. Patien
ts with severe neurotoxicity had significantly higher FK506 whole-bloo
d and plasma levels (31.3+/-6.8 ng/ml and 3.9+/-1.4 ng/ml) in comparis
on with patients with mild-to-moderate neurotoxicity (18.1+/-2.4 ng/ml
and 1.1+/-0.13 ng/ml) (P=0.048 and P<0.001, respectively). Long-term
use of FK506 was associated with a significant reduction in glomerular
filtration rate at 1-year posttransplant in patients on primary FK506
treatment (33%, P<0.001). The reduction in glomerular filtration rate
correlated with the yearly mean FK506 plasma but not with whole-blood
levels or FK506 dose. There was a correlation between FK506 whole-blo
od and plasma levels (r=0.713, P<0.001) but not between the levels (wh
ole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK
506 whole-blood and plasma levels were 14.1+/-0.26 ng/ml and 0.96+/-0.
75 ng/ml, respectively. There was a large intra- and interpatient vari
ability in the ratio between whole-blood and plasma levels (range 1.0-
73.5), with a mean ratio of 18.0+/-0.28 (+/-SEM). In conclusion, monit
oring of FK506 trough levels is of importance to avoid nephro- and neu
rotoxicity, but monitoring is only of limited help to avoid acute reje
ction. Monitoring of FK506 levels in plasma seems to be superior to th
at in whole blood.