Conversion of Stable Liver Transplant Recipients From a Twice Daily Prograf Based Regimen to a Once Daily Modified Release Tacrolimus Based Regimen

Pharmacokinetics of tacrolimus converted from twice-daily formulation to once-daily formulation in Chinese stable liver transplant recipients

“…The 90% CI for the ratio of MR/IR tacrolimus was 77%-90%, and the 90% CI for the ratio in dose-adjusted AUC 0-24 was only 66%-79%. These statistics are not in agreement with the previous report [9] , which showed that most patients did not require a dose adjustment when they were converted from IR to MR tacrolimus, and the 90% CI for the ratio in AUC 0-24 was within the equivalence range of 80%-125%. The discrepancy between these results and our fi ndings may be due to the difference in study design.…”

“…The discrepancy between these results and our fi ndings may be due to the difference in study design. The reported study [9] was a four-period replicate (IR tacrolimus-MR tacrolimus-IR tacrolimus-MR tacrolimus) design study in which treatment with tacrolimus was converted on three occasions, and each treatment period was only 14 d. However, the present study was a one-way conversion from twice-daily IR tacrolimus to once-daily MR tacrolimus, and it had a longer period at nearly three months of treatment.…”

“…Before our study, a set of clinical trials had been conducted to compare the PK profi les of tacrolimus between IR and MR formulations [9][10][11][12][13] . The clinical trial in de novo liver transplant patients showed that the systemic exposure AUC 0-24 on d 1 was approximately 50% lower for MR tacrolimus than for IR tacrolimus at equivalent doses, whereas values at steady state (d 14 and w 6) were similar for both formulations [13] .…”

“…The clinical trial in de novo liver transplant patients showed that the systemic exposure AUC 0-24 on d 1 was approximately 50% lower for MR tacrolimus than for IR tacrolimus at equivalent doses, whereas values at steady state (d 14 and w 6) were similar for both formulations [13] . The conversion study in stable liver transplant patients showed that the AUC 0-24 at steady state for MR tacrolimus once daily was equivalent to taking IR tacrolimus twice a day, but on average an 11% lower AUC 0-24 was found after a mg-for-mg dose conversion [9] . In order to better understand the PK profi les of MR tacrolimus, we performed a conversion study with a long period follow up in Chinese stable liver transplant recipients.…”

“…This formulation, known commercially as Advagraf, has been approved in more than 30 countries and regions as of 2010. The pharmacokinetics (PK) of tacrolimus have been compared between MR and IR formulations in stable kidney, liver, and heart transplant patients, and in de novo kidney and liver transplant recipients [9][10][11][12][13] . However, there is few clinical data on Chinese patients.…”