Tacrolimus whole blood concentrations correlate closely to side-effects in renal transplant recipients

Br J Clin Pharmacol. 1999 Sep;48(3):445-8. doi: 10.1046/j.1365-2125.1999.00007.x.

Abstract

Aims: To evaluate the relationship between tacrolimus whole blood concentrations and side-effects and rejections in 14 renal transplant recipients.

Methods: Tacrolimus was measured by MEIA in whole blood in samples collected repeatedly during the first year after transplantation. Retrospectively, tacrolimus trough concentrations on the days with adverse events (n=172) or rejection (n=28) were related to the total distribution of the concentration values (n=656).

Results: Side-effects (one or more) were noted in connection with 76% of tacrolimus concentrations above 30 ng ml-1, with 41% of concentrations within the interval of 20-30 ng ml-1, with 26% of the concentrations within the interval of 10-20 ng ml-1 and with only 5.3% on the concentrations lower than 10 ng ml-1. No relation to the tacrolimus concentration was seen for rejection episodes.

Conclusions: We conclude that therapeutic drug monitoring may be helpful in the management of tacrolimus therapy and that tacrolimus whole blood trough concentrations (MEIA) should preferably be kept below 20 ng ml-1 to avoid side-effects, such as nephro-and neurotoxicity and infections. The lower limit of the therapeutic range has yet to be defined.

MeSH terms

  • Adult
  • Aged
  • Drug Monitoring
  • Female
  • Graft Rejection / diagnosis
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / blood*
  • Kidney Transplantation* / adverse effects
  • Male
  • Middle Aged
  • Prognosis
  • Tacrolimus / adverse effects
  • Tacrolimus / blood*

Substances

  • Immunosuppressive Agents
  • Tacrolimus