A prolonged-release formulation of tacrolimus for once-daily administration (Tacrolimus QD) has been developed to offer potential improvements in patient adherence. This study compared the pharmacokinetics (PK) of tacrolimus in stable kidney transplant recipients before and after conversion from twice-daily tacrolimus (Tacrolimus BID) to Tacrolimus QD.
This was an open-label, multicenter replicate design study in stable adult kidney transplant recipients (≥6 months posttransplantation) maintained on Tacrolimus BID. Patients underwent four sequential 14-day treatment periods of alternating Tacrolimus BID and QD (mg:mg conversion). Four 24-hour PK profiles were collected, one on the last day of each treatment period. Adverse events were also reported.
A total of 60 of 69 patients completed all 4 PK profiles. Steady-state tacrolimus area under the curve from 0 to 24 hours and Cmin were comparable for both formulations, with treatment ratio means (90% confidence intervals) of 92.9% (89.8%–96.0%) and 90.9% (87.3%–94.6%), respectively (acceptance interval: 80%–125%). Both formulations were well tolerated, with renal function remaining stable over the 8-week period. There was a good correlation between area under the curve from 0 to 24 hours and Cmin for Tacrolimus QD and BID (r = 0.88 and 0.82, respectively). The relationship between these two parameters was also similar.
The results of this study provide evidence for safe conversion from Tacrolimus BID to QD with appropriate trough concentration monitoring.
From the *Department of Internal Medicine, Subdivision of Nephrology, University Hospital, Maastricht, the Netherlands; †Jacaranda Hospital, Pretoria, South Africa; ‡St Augustine's Hospital, Chelmsford Medical Centre, Durban, South Africa; §Christiaan Barnard Memorial Hospital, Cape Town, South Africa; ¶Department of Medicine, University of Stellenbosch and Tygerberg Hospital, Cape Town, South Africa; ‖Astellas GmbH, Munich, Germany (formerly Fujisawa, Germany at time of study); and **Astellas Pharma Europe Limited, Staines, United Kingdom.
Received for publication April 18, 2011; accepted December 1, 2011.
Astellas Pharma Europe Limited was formerly Fujisawa, Germany at time of study.
Supported by Astellas Pharma Europe Ltd, Staines, United Kingdom.
J. van Hooff has participated in trials sponsored by Astellas, Novartis and Roche, has received lecture fees from Astellas, Genzyme, and TEVA and has received research grants from Astellas and Roche. M. Christiaans has participated in trials sponsored by Astellas, Novartis, and Roche and has received research grants from Astellas and Roche. J. Kallmeyer, D. Miller, S. Dawood, M. Christiaans, I. Van der Walt have declared no conflicts of interest. C. Karpf was an employee of Astellas at the time of the study, and N. Undre is currently an employee of Astellas.
This study was conducted from 14 April 2003 to 20 December 2003, before the cut-off date for registration of new and ongoing clinical trials and, thus, it was not registered in a public trials registry. As the study results formed part of a regulatory development dossier, it was not possible to submit the study for full publication before now, although an abstract of the preliminary study results was presented soon after study completion at The 3rd International Congress on Immunosuppression (2004) in San Diego.
Correspondence: Nasrullah Undre, PhD, Astellas Pharma Europe Ltd, Lovett House, Lovett Road, Staines, Middlesex TW18 3AZ, UK (e-mail: Nas.email@example.com).