P1794CHANGES IN PHARMACOKINETIC PROFILE OF MYCOPHENOLATE MOFETIL AND TACROLIMUS IN THE TRANSPLANTED PATIENT AFTER BOWEL SURGERY: A PROSPECTIVE COHORT STUDY

Abstract

Abstract Background and Aims Considering the particular pharmacokinetic (PK) profile of mycophenolate (MMF/MPS) with the important contribution of enterohepatic recirculation (EHC) and the potential alteration in tacrolimus (TAC) exposure, a PK study in solid-organ transplant patients who had undergone intestinal resection was carried out. Method This is a prospective single-center study of MMF/MPS and TAC exposure changes after bowel resection and after reconstruction. Whole blood samples were collected at the following time points: 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose. Areas under the curves (AUCs) were determined in both conditions: with ileostomy and after bowel reconstruction. Results Six renal and two cardiac transplant recipients were included. Four subjects completed both pre- and post-reconstruction surgery procedures. Different intestinal anatomic resections were performed (Table 1). Patients with terminal ileostomy showed an under exposure to MMF/MPS. In three patients, initial MPA levels were on target, but they decreased >80% after 4 hours post-drug administration. After bowel reconstruction, the AUC increased maintaining MMF/MPA levels during 12h (Table 2). Before bowel reconstruction, TAC trough levels were within therapeutic target but, after reconstruction, AUCs normalized by dose were much higher than the expected. Conclusion Transplant recipients with ileostomy showed infra-exposure to mycophenolate. After 4 hours post-dose, MMF/MPA was undetectable because of the absence of EHC, which was recovered after anatomical correction. TAC exposure was higher after bowel reconstruction suggesting changes in the absorption. The use of mTORi in such clinical situations would be an alternative.