Relationships of tacrolimus pharmacokinetic measures and adverse outcomes in stable adult liver transplant recipients.
OBJECTIVE
Alternative measures to trough concentrations [non-trough concentrations and limited area under the concentration-time curve (AUC)] have been shown to better predict tacrolimus AUC. The aim of this study was to determine if these are also better predictors of adverse outcomes in long term liver transplant recipients.


METHODS
The associations between tacrolimus trough concentrations (C(0)), non-trough concentrations (C(1), C(2), C(4), C(6/8)), and AUC(0-12) and the occurrence of hypertension, hyperkalaemia, hyperglycaemia and nephrotoxicity were assessed in 34 clinically stable liver transplant patients.


CONCLUSIONS
The most common adverse outcome was hypertension, prevalence of 36%. Hyperkalaemia and hyperglycaemia had a prevalence of 21% and 13%, respectively. A sequential population pharmacokinetic/pharmacodynamic approach was implemented. No significant association between predicted C(0), C(1), C(2), C(4), C(6/8) or AUC(0-12) and adverse effects could be found. Tacrolimus concentrations and AUC measures were in the same range in patients with and without adverse effects.


CONCLUSIONS
Measures reported to provide benefit, preventing graft rejection and minimizing acute adverse effects in the early post-transplant period, were not able to predict adverse effects in stable adult liver recipients whose trough concentrations were maintained in the notional target range.
Dansirikul
C
C
School of Pharmacy, University of Queensland, Brisbane, Queensland 4072, Australia.
Staatz
C E
CE
Duffull
S B
SB
Taylor
P J
PJ
Lynch
S V
SV
Tett
S E
SE
D000328:Adult; D019540:Area Under Curve; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D006947:Hyperkalemia / Q000139:chemically induced; D006973:Hypertension / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007674:Kidney Diseases / Q000139:chemically induced; D016031:Liver Transplantation; D008297:Male; D008962:Models, Theoretical; D016559:Tacrolimus / Q000009:adverse effects* / Q000493:pharmacokinetics* / Q000627:therapeutic use
D007166:Immunosuppressive Agents; D016559:Tacrolimus