Introduction. Diabetic patients undergoing pancreas transplantation often experience a high incidence of gastroparetic gastropathy, which can lead to inadequate tacrolimus exposure. Our study aimed to compare tacrolimus exposure before and after early conversion from immediate-release tacrolimus (IR-Tac) to MeltDose prolonged-release tacrolimus (LCP-Tac) in recipients of simultaneous pancreas-kidney transplantation.
Methods. We conducted a prospective single-center crossover study involving 25 consecutive simultaneous pancreas-kidney recipients. Pharmacokinetic profiles of IR-Tac were determined 7-17 days post-transplantation. Subsequently, conversion to LCP-Tac was performed, and pharmacokinetic profiles were investigated 7-14 days later. LCP-Tac was further retained for the total duration of the study (6 months). The primary outcome was tacrolimus exposure as reflected by AUC 0-24h with IR-Tac compared to LCP-Tac. Secondary outcomes included correlation between AUC 0-24h and tacrolimus trough levels, incidence of rejection episodes, and allograft function at 6 months.
Results. Twenty-three patients were included in the final analysis. At 6 months, all pancreases exhibited optimal function (defined according to Igls 2.0), except for two cases of early failure due to complete thrombosis. We observed an increase in AUC 0-24h following the switch to LCP-Tac compared to IR-Tac (AUC 0-24h = 233 vs 265 h.ng/ml, p = 0.05), despite a significant reduction in the daily dose (7.7mg/d vs 9.15 mg/d). There was an improved correlation between AUC 0-24h and tacrolimus trough levels with LCP-Tac, suggesting that tacrolimus trough levels better reflect AUC when using LCP-Tac compared to IR-Tac. No episodes of pancreas rejection were observed during the study follow-up.
Conclusion. Our findings support early conversion from IR-Tac to LCP-Tac for stable pancreas transplant recipients, improving tacrolimus exposure with a total dose reduction, without improving the risk of rejection.