The Pharmacokinetics of Enteric-Coated Mycophenolate Sodium and Its Gastrointestinal Side Effects in De Novo Renal Transplant Recipients of Hispanic Ethnicity

Objective: The aim of the study is to characterize the pharmacokinetics and the gastrointestinal side effect profiles of enteric-coated mycophenolate sodium (EC-MPS) in de novo kidney transplant patients of Hispanic ethnicity. Materials and Methods: The pharmacokinetic study of EC-MPS was conducted in 11 de novo kidney transplant patients of Hispanic ethnicity. Eight blood samples were obtained after EC-MPS was given at the steady state. Blood concentrations of mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) were measured. Results: The mean age (+/- standard deviation) was 39.4 (+/- 12.3) years. The mean daily dose of EC-MPS at the time of the pharmacokinetic study was 1408 +/- 108 mg. For MPA and MPAG, the time to peak concentration was 2.5 +/- 1.3 hours and 4.6 +/- 3.1 hours, respectively; the peak concentration (C-max) was 19.3 +/- 17.2 mg/L and 109.4 +/- 49.2 mg/L; and the area under the curve from 6 to 12 hours (AUC(6-12)) was 32.2 +/- 19.3 mg.hr/L and 373.7 +/- 235.8 mg.hr/L, respectively, which represents 41.3% and 43.0% of AUC(0-12). The AUC(0-12) for MPA measured 77.8 +/- 53.1 mg.hr/L and for MPAG 869.2 +/- 388.8 mg.hr/L. Seven patients (64%) exhibited a second peak at approximately 8.3 hours after the dose at a mean concentration (6 standard deviation) of 10.3 +/- 7.6 mg/L. The C-max or AUC of MPA does not correlate with overall Gastrointestinal Symptom Rating Scale scores or subscale scores, but the C-max of MPAG correlates with indigestion subscale (P = 0.022), diarrhea (P = 0.032), and overall scores (P = 0.028). The AUC of MPAG also correlates with acid reflux (P = 0.024) and indigestion (P = 0.032). Discussion and Conclusion: The pharmacokinetics of EC-MPS has a high variability in de novo kidney transplant patients of the Hispanic ethnicity, which was similar to other ethnic groups. The MPA exposure expressed by the AUC appears to be higher in Hispanic patients than those reported in other ethnic groups, which may be the result of various factors such as difference of the uridine diphosphate glucuronosyltransferase enzyme genotypes, but gastrointestinal side effects were acceptable and the C-max or AUC of MPAG showed correlations with gastrointestinal symptoms.