Skip to main content
SpringerLink
Log in

Pharmacokinetics of tacrolimus in stable paediatric renal transplant recipients

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Because tacrolimus (Tac) has a narrow therapeutic index and highly inter- and intra-individual variable pharmacokinetic (PK) characteristics, monitoring of drug exposure is recommended, but limited data are available on the kinetics of Tac in paediatric renal transplant recipients, especially of limited sampling strategies. To investigate the correlation between Tac trough level (TL) and the 0–12 h area under the curve (AUC), and the value of abbreviated AUC monitoring, we evaluated 12 h PK profiles in 27 children at least 1 year after transplantation. There was a significant discrepancy between Tac TLs and 0–12 h AUC (r = 0.60). Every time point, different from C0, gave a better prediction for the drug exposure, with C4 and C6 as best predictors (r = 0.93 and r = 0.92, respectively). The 0–12 h AUC was estimated with great precision by the use of a two- or three-point sampling strategy, and the latter is more time-point independent. In paediatric renal transplant recipients on Tac maintenance therapy, whose condition is stable, Tac TL is not a reliable tool for the estimation of drug exposure. Abbreviated monitoring, especially at three points in time, give reliable predictions of the complete 0–12 h AUC. We suggest a 0–12 h AUC of around 150 ng × h/ml for stable paediatric renal transplant recipients 1 year after transplantation and around 100 ng × h/ml in the following years. Target AUC values should be further established for paediatric transplant recipients according to the time after transplantation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Conley SB, Flechner SM, Rose G, Van Buren CT, Brewer E, Kahan BD (1985) Use of cyclosporine in pediatric renal transplant recipients. J Pediatr 106:45–49

    Article  CAS  Google Scholar 

  2. Hardie IR, Tiller DJ, Mahony JF, Miach PJ, Thomson NM, Thatcher GN, Rigby RJ, Menzies BL (1993) Optimal combination of immunosuppressive agents for renal transplantation: first report of a multicentre, randomised trial comparing cyclosporine + prednisolone with cyclosporine + azathioprine and with triple therapy in cadaver renal transplantation. The Australian Collaborative Trials Committee. Transplant Proc 25:583–584

    CAS  PubMed  Google Scholar 

  3. Starzl TE, Todo S, Fung J, Demetris AJ, Venkataramman R, Jain A (1989) K 506 for liver, kidney, and pancreas transplantation. Lancet 2:1000–1004

    Article  CAS  Google Scholar 

  4. Starzl TE, Fung J, Jordan M, Shapiro R, Tzakis A, McCauley J, Johnston J, Iwaki Y, Jain A, Alessiani M, Todo S (1990) Kidney transplantation under FK 506. JAMA 264:63–67

    Article  CAS  Google Scholar 

  5. Wallemacq PE, Verbeeck RK (2001) Comparative clinical pharmacokinetics of tacrolimus in paediatric and adult patients. Clin Pharmacokinet 40:283–295

    Article  CAS  Google Scholar 

  6. Filler G, Webb NJ, Milford DV, Watson AR, Gellermann J, Tyden G, Grenda R, Vondrak K, Hughes D, Offner G, Griebel M, Brekke IB, McGraw M, Balzar E, Friman S, Trompeter R (2005) Four-year data after pediatric renal transplantation: a randomized trial of tacrolimus vs. cyclosporin microemulsion. Pediatr Transplant 9:498–503

    Article  CAS  Google Scholar 

  7. Filler G, Grygas R, Mai I, Stolpe HJ, Greiner C, Bauer S, Ehrich JH (1997) Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants. Nephrol Dial Transplant 12:1668–1671

    Article  CAS  Google Scholar 

  8. Lee MN, Butani L (2007) Improved pharmacokinetic monitoring of tacrolimus exposure after pediatric renal transplantation. Pediatr Transplant 11:388–393

    Article  CAS  Google Scholar 

  9. Armendáriz Y, Pou L, Cantarell C, Lopez R, Perelló M, Capdevila L (2005) Evaluation of a limited sampling strategy to estimate area under the curve of tacrolimus in adult renal transplant patients. Ther Drug Monit 27:431–434

    Article  Google Scholar 

  10. Op den Buijsch RA, van de Plas A, Stolk LM, Christiaans MH, van Hooff JP, Undre NA, van Dieijen-Visser MP, Bekers O (2007) Evaluation of limited sampling strategies for tacrolimus. Eur J Clin Pharmacol 63:1039–1044

    Article  CAS  Google Scholar 

  11. Derksen-Lubsen G, Van Steensel-Moll HA, Visser HK (2006) Compendium kindergeneeskunde diagnostiek en behandeling. Bohn Stafleu Van Loghum, Houten, p 325

  12. Kuypers D, de Jonge H, Naesens M, Lerut E, Verbeke K, Vanrenterghem Y (2007) CYP3A5 and CYP3A4 but not MDR1 single-nucleotide polymorphisms determine long-term tacrolimus disposition and drug-related nephrotoxicity in renal recipients. Clin Pharmacol Ther 82:711–725

    Article  CAS  Google Scholar 

  13. Staatz CE, Willis C, Taylor PJ, Tett SE (2002) Population pharmacokinetics of tacrolimus in adult kidney transplant recipients. Clin Pharmacol Ther 72:660–669

    Article  CAS  Google Scholar 

  14. Filler G, Feber J, Lepage N, Weiler G, Mai I (2002) Universal approach to pharmacokinetic monitoring of immunosuppressive agents in children. Pediatr Transplant 6:411–418

    Article  CAS  Google Scholar 

  15. Kim JS, Aviles DH, Silverstein DM, Leblanc PL, Matti Vehaskari V (2005) Effect of age, ethnicity, and glucocorticoid use on tacrolimus pharmacokinetics in pediatric renal transplant patients. Pediatr Transplant 9:162–169

    Article  CAS  Google Scholar 

  16. Shishido S, Asanuma H, Tajima E, Honda M, Nakai H (2001) Pharmacokinetics of tacrolimus in pediatric renal transplant recipients. Transplant Proc 33:1066–1068

    Article  CAS  Google Scholar 

  17. Webb NJ, Stevenson PJ, Lewis MA, Postlethwaite RJ, Bradbury MG, Undre NA (2002) Pharmacokinetics of tacrolimus in paediatric renal transplant recipients. Transplant Proc 34:1948–1950

    Article  CAS  Google Scholar 

  18. Montini G, Ujka F, Varagnolo C, Ghio L, Ginevri F, Murer L, Thafam BS, Carasi C, Zacchello G, Plebani M (2006) The pharmacokinetics and immunosuppressive response of tacrolimus in paediatric renal transplant recipients. Pediatr Nephrol 21:719–724

    Article  Google Scholar 

  19. Scholten EM, Cremers SC, Schoemaker RC, Rowshani AT, van Kan EJ, den Hartigh J, Paul LC, de Fijter JW (2005) AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients. Kidney Int 67:2440–2447

    Article  CAS  Google Scholar 

  20. Kelles A, Herman J, Tjandramaga TB, Van Damme-Lombaerts R (1999) Sandimmune to Neoral conversion and value of abbreviated AUC monitoring in stable pediatric kidney transplant recipients. Pediatr Transplant 3:282–287

    Article  CAS  Google Scholar 

  21. Knight SR, Morris PJ (2007) The clinical benefits of cyclosporine C2-level monitoring: a systematic review. Transplantation 83:1525–1535

    Article  CAS  Google Scholar 

  22. Jorgensen K, Povlsen J, Madsen S, Madsen M, Hansen H, Pedersen A, Heinsvig EM, Poulsen J (2002) C2 (2-h) levels are not superior to trough levels as estimates of the area under the curve in tacrolimus-treated renal-transplant patients. Nephrol Dial Transplant 17:1487–1490

    Article  CAS  Google Scholar 

  23. Opelz G, Döhler B (2008) Effect on kidney graft survival of reducing or discontinuing maintenance immunosuppression after the first year posttransplant. Transplantation 86:371–376

    Article  Google Scholar 

  24. Hesselink DA, Ngyuen H, Wabbijn M, Gregoor PJ, Steyerberg EW, van Riemsdijk IC, Weimar W, van Gelder T (2003) Tacrolimus dose requirement in renal transplant recipients is significant higher when used in combination with corticoids. Br J Clin Pharmacol 56:327–330

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Paediatric Medicine, University Hospital Leuven, Herestraat 49, Louvain, 3000, Vlaams-Brabant, Belgium

    Tania Claeys

  2. Pediatric Nephrology and Organ Transplantation, University Hospital Leuven, Louvain, Belgium

    Maria Van Dyck & Rita Van Damme-Lombaerts

Authors
  1. Tania Claeys
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Van Dyck
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rita Van Damme-Lombaerts
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tania Claeys.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Claeys, T., Van Dyck, M. & Van Damme-Lombaerts, R. Pharmacokinetics of tacrolimus in stable paediatric renal transplant recipients. Pediatr Nephrol 25, 335–342 (2010). https://doi.org/10.1007/s00467-009-1331-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-009-1331-6

Keywords

Search

Navigation