FK506 trough levels in whole blood and plasma in liver transplant recipients: Correlation with clinical events and side effects

L. Backman, M. Nicar, M. Levy, D. Distant, C. Eisenstein, T. Renard, R. Goldstein, B. Husberg, T. A. Gonwa, G. Klintmalm

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Abstract

FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity 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 levels within the same range as patients with stable liver function. Patients with severe neurotoxicity had significantly higher FK506 whole-blood and plasma levels (31.3 ± 6.8 ng/ml and 3.9 ± 1.4 ng/ml) in comparison 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-blood and plasma levels (r=0.713, P < 0.001) but not between the levels (whole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK506 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 variability 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, monitoring of FK506 trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring is only of limited help to avoid acute rejection. Monitoring of FK506 levels in plasma seems to be superior to that in whole blood.

Original languageEnglish (US)
Pages (from-to)519-525
Number of pages7
JournalTransplantation
Volume57
Issue number4
StatePublished - 1994
Externally publishedYes

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Tacrolimus
Liver
Glomerular Filtration Rate
Transplant Recipients
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Backman, L., Nicar, M., Levy, M., Distant, D., Eisenstein, C., Renard, T., ... Klintmalm, G. (1994). FK506 trough levels in whole blood and plasma in liver transplant recipients: Correlation with clinical events and side effects. Transplantation, 57(4), 519-525.

FK506 trough levels in whole blood and plasma in liver transplant recipients : Correlation with clinical events and side effects. / Backman, L.; Nicar, M.; Levy, M.; Distant, D.; Eisenstein, C.; Renard, T.; Goldstein, R.; Husberg, B.; Gonwa, T. A.; Klintmalm, G.

In: Transplantation, Vol. 57, No. 4, 1994, p. 519-525.

Research output: Contribution to journalArticle

Backman, L, Nicar, M, Levy, M, Distant, D, Eisenstein, C, Renard, T, Goldstein, R, Husberg, B, Gonwa, TA & Klintmalm, G 1994, 'FK506 trough levels in whole blood and plasma in liver transplant recipients: Correlation with clinical events and side effects', Transplantation, vol. 57, no. 4, pp. 519-525.
Backman, L. ; Nicar, M. ; Levy, M. ; Distant, D. ; Eisenstein, C. ; Renard, T. ; Goldstein, R. ; Husberg, B. ; Gonwa, T. A. ; Klintmalm, G. / FK506 trough levels in whole blood and plasma in liver transplant recipients : Correlation with clinical events and side effects. In: Transplantation. 1994 ; Vol. 57, No. 4. pp. 519-525.
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abstract = "FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity 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 levels within the same range as patients with stable liver function. Patients with severe neurotoxicity had significantly higher FK506 whole-blood and plasma levels (31.3 ± 6.8 ng/ml and 3.9 ± 1.4 ng/ml) in comparison 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-blood and plasma levels (r=0.713, P < 0.001) but not between the levels (whole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK506 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 variability 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, monitoring of FK506 trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring is only of limited help to avoid acute rejection. Monitoring of FK506 levels in plasma seems to be superior to that in whole blood.",
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T1 - FK506 trough levels in whole blood and plasma in liver transplant recipients

T2 - Correlation with clinical events and side effects

AU - Backman, L.

AU - Nicar, M.

AU - Levy, M.

AU - Distant, D.

AU - Eisenstein, C.

AU - Renard, T.

AU - Goldstein, R.

AU - Husberg, B.

AU - Gonwa, T. A.

AU - Klintmalm, G.

PY - 1994

Y1 - 1994

N2 - FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity 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 levels within the same range as patients with stable liver function. Patients with severe neurotoxicity had significantly higher FK506 whole-blood and plasma levels (31.3 ± 6.8 ng/ml and 3.9 ± 1.4 ng/ml) in comparison 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-blood and plasma levels (r=0.713, P < 0.001) but not between the levels (whole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK506 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 variability 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, monitoring of FK506 trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring is only of limited help to avoid acute rejection. Monitoring of FK506 levels in plasma seems to be superior to that in whole blood.

AB - FK506 trough levels were measured by ELISA in paired whole-blood and plasma samples in 59 liver transplant recipients. Patients with nephrotoxicity 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 levels within the same range as patients with stable liver function. Patients with severe neurotoxicity had significantly higher FK506 whole-blood and plasma levels (31.3 ± 6.8 ng/ml and 3.9 ± 1.4 ng/ml) in comparison 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-blood and plasma levels (r=0.713, P < 0.001) but not between the levels (whole blood or plasma) and FK506 dose (mg/day or mg/kg/day). The mean FK506 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 variability 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, monitoring of FK506 trough levels is of importance to avoid nephro- and neurotoxicity, but monitoring is only of limited help to avoid acute rejection. Monitoring of FK506 levels in plasma seems to be superior to that in whole blood.

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