Impact of Colectomy with Ileostomy in Immunosuppression Management after Heart Transplantation Mycophenolate Mofetil Levels Secondary to Ileostomy

Abstract

Introduction The management of immunosuppressants constitutes a challenge in clinical practice to maintain drug exposure within therapeutic target because of its variable pharmacokinetics. Case Report A 38 years-old male with an advanced non-compacted cardiomyopathy underwent orthotopic heart transplantation (OHT). On the 4th day post-op he developed a paralytic ileum complicated with cecum perforation and faecaloid peritonitis that required emergent right hemicolectomy and terminal ileostomy. At discharge, his treatment was tacrolimus, mycophenolate mofetil (MMF) and prednisone.During follow-up pre-dose mycophenolic acid (MPA) levels were undetectable despite ensuring good adherence and increased MMF dose. Meanwhile, tacrolimus levels were on target. A pharmacokinetic study with area under concentration-time (AUC) evidenced absence of MPA levels after 4h from oral administration. Everolimus was introduced in substitution of MMF because of this, achieving adequate pre-dose concentration levels. After per-protocol intestine reconstruction with ileocolonic anastomosis, a new MPA pharmacokinetic curve was obtained. MPA dose adjusted AUC was 51% higher post correction. Concentration curves pre and post corrective surgery are presented (figure 1). Discusion MMF and its active metabolite MPA are rapidly absorbed resulting in a high oral bioavailability. Yet, because of enterohepatic circulation (EHC), a second rise in MPA plasmatic concentrations appears after 4-8h of its administration, contributing to 10-60% of the total AUC exposure. In patients with ileostomy, the lack of EHC causes a complete absence of MPA levels after 4h of oral administration and thus, an ulterior undetectable Cmin. Summary Patients with ileostomy and OHT may be at risk of rejection given the lack of EHC of MPM. Therapeutic monitoring of MPA with AUC or conversion to other immunosuppressants should be considered in this population.