Dosing strategies for once-daily extended release tacrolimus in kidney transplant recipients based on genotype.

BACKGROUND

Tacrolimus extended-release tablets have been Food and Drug Administration-approved for use in the kidney transplant population. Dosing requi rements often vary for tacrolimus based on several factors including variation in metabolism based on expression. Patients who express often require higher dosing of immediate-release tacrolimus, but this has not been established for tacrolimus extended-release tablets in the setting.

AIM

To obtain target trough concentrations of extended-release tacrolimus in kidney transplant recipients according to genotype.

METHODS

Single-arm, prospective, single-center, open-label, observational study (ClinicalTrials.gov: NCT037 13645). Life cycle pharma tacrolimus (LCPT) orally once daily at a starting dose of 0.13 mg/kg/day based on actual body weight. If weight is more than 120% of ideal body weight, an adjusted body weight was used. LCPT dose was adjusted to maintain tacrolimus trough concentrations of 8-10 ng/mL. Pharmacogenetic analysis of genotype was performed at study conclusion.

RESULTS

Mean time to therapeutic tacrolimus trough concentration was longer in intermediate and extensive metabolizers non-expressers (6 d 13.5 d 4.5 d; = 0.025). Mean tacrolimus doses and weight-based doses to achieve therapeutic concentration were higher in intermediate and extensive metabolizers non-expressers (16 mg 16 mg 12 mg; = 0.010) (0.20 mg/kg 0.19 mg/kg 0.13 mg/kg; = 0.018). extensive metabolizers experienced lower mean tacrolimus trough concentrations throughout the study period compared to intermediate metabolizers and non-expressers (7.98 ng/mL 9.18 ng/mL 10.78 ng/mL; = 0 0.008). No differences were identified with regards to kidney graft function at 30-d post-transplant. Serious adverse events were reported for 13 (36%) patients.

CONCLUSION

Expression of leads to higher starting doses and incremental dosage titration of extended-release tacro limus to achieve target trough concentrations. We suggest a higher starting dose of 0.2 mg/kg/d for expressers.