Aims: To analyze the differences in mycophenolic acid (MPA) pharmacokinetics and digestive side effects in renal transplant recipients on treatment with Mycophenolate mofetil (MMF) and Mycophenolate sodium (EC-MPS) in patients carrying UGT1A9 polymorphism.

Methods: UGT1A9, C-2152-T and T-275-A Single nucleotide polymorphisms (SNP) were studied in renal transplant recipients. The value of the 12-hour area under the curve (AUC0-12h) was determined as follows: baseline (before administration of the morning dose), and after 30, 60, 90, 120, 150, 180 and 210 minutes y afterwards at 4, 5, 6, 8, 10 y 12 hours. Gastrointestinal symptoms were evaluated through validated surveys; Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index.

Results: In patients carrying UGT 1A9 gene polymorphism a greater area under the curve was observed when treated with EC-MPS (65.9 mg/l/h) compared to AUC0-12h with MMF (53.9 mg/l/h) (p=0.05). A double pharmacokinetic study was done to 27 patients. In the first study they were treated with MMF and in the second they were converted to an equivalent dose of EC-MPS. In patients carrying UGT1A9 gene polymorphism a greater area under the curve was observed when treated with EC-MPS (64.9 mg/l/h ± 22.7) compared to MMF (55.4mg/l/h±14.0) (p=0.015). These differences weren't observed in patients without SNP. Regarding the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index, when results were analyzed according to whether their associated treatment was EC-MPS or MMF and carried SNP, we observed that for SNP carriers the scores were higher (the higher the score, the better their quality of life) in patients with EC-MPS (106, from 100-110), compared to those receiving MMF (105, from 103-107) (p=0.039). Conclusions: In presence of UGT1A9 gene polymorphism, MPA pharmacokinetics varies according to whether the patient is treated with MMF or EC-MPS, obtaining a greater area under the curve for MPA when EC-MPS is administered. Likewise, we observed better scores for gastrointestinal symptoms and patients' quality of life in gene polymorphism carriers when they are on treatment with EC-MPS. This finding is probably due to the delayed release of EC-MPS that could make up for the higher drug metabolism associated with UGT enzyme polymorphism.

CITATION INFORMATION: Calvo Romero N, Perez-Flores I, Shabaka A, Moreno De La Higuera M, Rodriguez-Cubillo B, Delgado J, Calvo M, Lopez De La Manzanara V, Sanchez-Fructuoso A. Benefits of Mycophenolate Sodium Over Mycophenolate Mofetil in Renal Transplant Patients Carrying UGT1A9 Polymorphism. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress