Pharmacokinetics for Once- Versus Twice-Daily Tacrolimus Similar in De Novo Kidney Transplant Recipients: Presented at TTS

To print: Select File and then Print from your browser's menu
---------------------------------------------------------------------------------------
Title: Pharmacokinetics for Once- Versus Twice-Daily Tacrolimus Similar in De Novo Kidney Transplant Recipients: Presented at TTS
URL: http://www.pslgroup.com/dg/2286CA.htm
Doctor's Guide
August 13, 2008

By Rachel Parratt

SYDNEY, Australia -- August 13, 2008 -- Results of a phase 3 substudy show strong pharmacokinetic (PK) correlation between once-daily, prolonged-release (PR) tacrolimus (Advagraf) and twice-daily tacrolimus (Prograf) at 3 days post-transplant in de novo kidney recipients.

Nasrullah Undre, PhD, Astellas Pharma Europe, London, United Kingdom, presented the findings on August 13 at the 22nd International Congress of the Transplantation Society (TTS 2008).

A total of 44 patients were included in the 2-week subanalysis of the phase 3 study investigating the PK of tacrolimus for once-daily PR versus twice-daily during the first 2 weeks (days 1, 3, 7, and 14) post-transplant.

Patients were randomised to either tacrolimus QD (n = 22) or BID (n = 22), and all patients provided 4 evaluable PK profiles (17 samples over 24 hours).

When area under the curve (AUC) between 0 and 24 hours was adjusted for dose between treatments, mean exposure was approximately 24% lower with the once-daily PR dose compared with the twice-daily dose on day 1 but was similar between groups by day 3. These findings suggest that differences observed between the 2 formulations on day 1 normalised 3 to 7 days post-transplant.

This initial exposure between tacrolimus QD and BID was lower than previously reported in the phase 2 study (32%) because of the initiation of tacrolimus before surgery.

When normalised for a dose of 0.1 mg/kg QD in both treatment groups, the ratio of means for AUC between 0 and 24 hours for once-daily PR tacrolimus was 75.96% (95% confidence interval [CI], 52.38-99.53) on day 1 and 107.82% (95% CI, 77.24-138.40) on day 3 compared with 99.60% (95% CI, 61.49-137.71) on day 7 for twice-daily tacrolimus.

"These results demonstrate that trough levels can be used as a surrogate measure of systemic exposure in clinical practice, and the same monitoring concept can be used for both formulations," said Dr. Undre.

Funding for this study was provided by Astellas.

[Presentation title: Pharmacokinetics (PK) of Tacrolimus for a Once Daily Prolonged Release Formulation (Advagraf) Versus Twice Daily (Prograf) in De Novo Kidney Transplant Recipients in a Phase III Multicentre Study. Mini-Oral Session 1WMO18]

http://www.docguide.com

Return to News Story Page

webmaster@pslgroup.com