The influence of various metabolic surgery procedures on immunosuppressant pharmacokinetics (PK) is largely unknown. For laparoscopic sleeve gastrectomy (LSG) (currently the most common procedure) no data exists. The purpose of this study was to evaluate single-dose PK of mycophenolate mofetil (MMF) in combination with two formulations of tacrolimus (Astagraf XL® and Prograf®) following LSG in end stage renal disease (ESRD) patients (pts) awaiting renal transplantation.

An open label, randomized, two-way crossover PK study was conducted under fasting conditions in adult, renal transplant candidates with ESRD at least 3 months post-LSG. MMF 1000mg every 12 hrs was administered in combination with either Astagraf XL 8mg daily or Prograf® 4mg every 12 hrs during the 24 hr study period. Genotyping was performed for several polymorphisms (UGT1A9-440C>T, UGT1A9-275T>A, UGT2B7-900A>G, and MRP2-24T>C) relevant to MMF PK. PK results were compared with previously published data.

23 subjects completed the study. Mean age was 50.8 years (+11.4); the majority were Caucasian (56.5%), male (56.5%), and hemodialysis-dependent (86.9%). Mean exposure to the active moiety, mycophenolic acid (MPA), described by MPA AUC_0-24was 37.48 ± 19.5 mg*h/L. This was within the recommended therapeutic range (MPA AUC of 30-60 mg*h/L). Inter- and intra-subject variability in MPA AUC were comparable with other single-dose studies in normal volunteers and ESRD pts^1,2. However, less variability was observed following LSG when compared with pts following gastric bypass, a more disruptive gastrointestinal procedure³. Actual body weight (R²=0.39) and ideal body weight (R²=0.24) did not predict MPA AUC_0-24. MPA PK profiles were similar when given with each of the two tacrolimus formulations (AUC_0-24 with Astagraf 35.98 mg*h/L vs. Prograf 37.48 mg*h/L, p=0.32). Genetic polymorphisms tested were not significant predictors of interindividual variability in this single-dose analysis.

MPA exposure following LSG in renal transplant candidates was within the target therapeutic range. A suggested approach to MMF dosing following LSG would be to initiate 1000 mg twice daily and adjust based on MPA AUC and toxicity.

1. Zhang, Q et al. Clin Ther. 2010; 32(1):171-8.

2. MacPhee IAM, et al. Kidney Int. 2000; 57(3):1164-8.

3. Rogers CC, et al. Clin Transplant 2008; 22:281-291.

CITATION INFORMATION: Leino A, Lichvar A, Kaiser T, Christians U, Mizuno T, Fukuda T, Alloway R, Vinks A, Woodle E, Diwan T. Mycophenolate Mofetil Single Dose Pharmacokinetics Following Laparoscopic Sleeve Gastrectomy. Am J Transplant. 2016;16 (suppl 3).

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