Background:

Tacrolimus extended-release (XL) is utilized in many immunosuppressive regimens post-kidney transplantation. Current dosing recommendation for the XL formulation in renal transplant (txp) is 0.15 mg/kg/day administered once daily. There is no literature currently available comparing various dosing weights to determine which leads to therapeutic concentrations most effectively in obese patients. The primary objective of this study was to determine the best method of dosing tacrolimus (TAC) XL for obese kidney txp recipients.

Methods:

In a prospective study design, de novo obese kidney txp recipients were randomized to receive TAC 0.15 mg/kg/day based on either IBW or aBW (IBW + 0.4 [actual BW – IBW]) starting on post-op day (POD) 0-2. Subsequent doses were adjusted to maintain a trough level of 8-12ng/ml. Post-txp patients underwent 3 pharmacokinetic assessments over a 14-day period. Study Day 1, 7, and 14 PK blood sampling points included: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours. The primary endpoint was the difference in TAC exposure (AUC24) in obese patients dosed using aBW compared to IBW. The secondary endpoint was the difference in the time to a therapeutic TAC trough level in the aBW compared to the IBW group. AUC assessment will be calculated using WinNonlin.

Results:

A total of 19 obese renal transplant recipients were randomized to participate in the study (9 aBW arm and 10 IBW arm). Baseline characteristics and demographics were not significantly different between the 2 groups except there was a larger proportion of Caucasian patients in the IBW compared to aBW arm (70% vs 22%; P = 0.04). Initial TAC doses were significantly different (14.4 vs. 10.1, p=0.001) Results of the primary outcome (AUC24) assessment are pending. There was no difference in the number of days to therapeutic trough concentration between the 2 groups (aBW=5.3, IBW=4.9 days; P=0.80). There was no difference in renal function between the 2 arms at discharge, 3, or 6 months.

Conclusions:

In a population of obese renal transplant recipients, initial doses of TAC XL based on IBW or aBW resulted in similar levels at POD 0-2, 5, and 14. Both dosing regimens provided similar renal function outcomes. AUC24 results will delineate whether there are differences in TAC exposure when calculating the initial dose using aBW vs IBW.

CITATION INFORMATION: Jasiak N, Thielke J, Progar K, Chen J, Adams C, Benedetti E, West-Thielke P. An Analysis of Tacrolimus XL Dosing in Obese Kidney Transplant Recipients. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress