Trough level from twice daily to once daily tacrolimus in early conversion kidney transplant recipients: a prospective study
- 336 Downloads
Background Early conversion from twice-daily tacrolimus (TAC-BID) to once-daily tacrolimus (TAC-OD) provides a greater benefit of reducing under-exposure of TAC-OD during the first period after transplantation. Information regarding the conversion dose among Asian kidney transplant recipients is still limited. Objective This study aimed to compare the trough levels (Cmin) of TAC-BID (Prograf®) and TAC-OD (Advagraf®). The values were obtained from early conversion intervention by 1:1 milligram per-milligram. Setting A university-based hospital. Method This study employed a single-center, open-label, prospective and single-armed design. Fifteen de novo standard risk kidney transplant recipients were enrolled. Fourteen days after transplantation, the Cmin of TAC-BID (pre-conversion Cmin) was determined. Subsequently, TAC-BID was converted to TAC-OD with a similar dose. The Cmin of TAC-OD was first measured at a steady state (immediate post-conversion Cmin) and compared. All enrolled patients received therapeutic monitoring at the first and second months. Main outcome measure Pre-conversion Cmin of TAC-BID and immediate post-conversion Cmin of TAC-OD. Results The immediate post-conversion Cmin was found to be 23% lowered than the pre-conversion Cmin. However, the Cmin of TAC-OD was found to be similar to the pre-conversion Cmin compared during the follow-up period. Renal function was found to be stable in all patients over 2 months. Conclusion Early conversion therapy was associated with a significantly lower immediate post-conversion Cmin but comparable Cmin throughout the follow-up period. The “one to one conversion ratio” from TAC-BID to TAC-OD could be performed among Asian de novo kidney transplant recipients at an early period after transplantation.
KeywordsEarly conversion Formulation Kidney transplant Tacrolimus Trough level
The authors would like to thank Supatat Chumnumwat, PharmD, BCPS, for his assistance in drafting the manuscript. Special thanks go to Stephen Pinder and Thomas McManamon for English editing. We also wish to thank Pitchaya Dilokpattanamongkol, BCPS, BCCP, for her helpful suggestion.
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Conflicts of interest
The authors have no conflicts of interest to declare.
- 8.Tsuchiya T, Ishida H, Tanabe T, Shimizu T, Honda K, Omoto K, et al. Comparison of pharmacokinetics and pathology for low-dose tacrolimus once-daily and twice-daily in living kidney transplantation: prospective trial in once-daily versus twice-daily tacrolimus. Transplantation. 2013;96(2):198–204.CrossRefPubMedGoogle Scholar
- 9.European Medicines Agency (EMA). Guideline on the investigation of bioequivalence. 2010. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/01/WC500070039.pdf. Accessed 1 Sep 2017.
- 11.Glowacki F, Lionet A, Hammelin JP, Labalette M, Provot F, Hazzan M, et al. Influence of cytochrome P450 3A5 (CYP3A5) genetic polymorphism on the pharmacokinetics of the prolonged-release, once-daily formulation of tacrolimus in stable renal transplant recipients. Clin Pharmacokinet. 2011;50(7):451–9.CrossRefPubMedGoogle Scholar
- 13.Abbott Laboratories, Diagnostics Division, Abbott Park, IL, Architect System, Tacrolimus, Ref 1 L77.Google Scholar
- 20.Yaowakulpatana K, Vadcharavivad S, Ingsathit A, Areepium N, Kantachuvesiri S, Phakdeekitcharoen B, et al. Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation. Eur J Clin Pharmacol. 2016;72(3):277–83.CrossRefPubMedGoogle Scholar
- 23.European Medicines Agency (EMA). Envarsus (tacrolimus extended release tablets): EU summary of product characteristics. 2014. http://www.ema.europa.eu/. Accessed 1 Sep 2017.
- 24.Medicines Evaluation Board in the Netherlands. Public assessment report: tacrolimus sandoz 0.5 mg, 1 mg and 5 mg, capsules, hard Sandoz B.V. 2010. http://db.cbg-meb.nl/Pars/h102100.pdf. Accessed 1 Sep 2017.