Coadministration of tacrolimus and mycophenolate mofetil in stable kidney transplant patients: Pharmacokinetics and tolerability

The tolerance and pharmacokinetics (PK) of tacrolimus (T) by the addition o f mycophenolate mofetil (MMF) in stable kidney transplant patients (6/group ) on long-term tacrolimus-based therapy were investigated. Patients receive d combination T and MMF therapy at three MMF doses: 1, 1.5, and 2 g/day adm inistered twice daily. A 12-hour blood PK profile for T was obtained prior to MMF dosing; concomitant 12-hour profiles for T mycophenolic acid (MPA), and mycophenolic acid glucuronide (MPAG) were obtained after 2 weeks of adm inistration. Tolerance was monitored through 3 months. The intra- and inter group PK of T were variable. The mean AUC(0-12) of T for each group was inc reased after 2 weeks of concomitant MMF administration, but the increase wa s not statistically significant. Both drugs were well tolerated. Gastrointe stinal events were of interest as such have been attributed to both T and M MF. Events reported were diarrhea, nausea, dyspepsia, and vomiting. Other c ommon adverse events were headache, hy pomagnesemia, and tremors. Most were mild, although a few were considered to be moderate. There was no apparent relationship between the incidence of any adverse event and MMF treatment group. In the present study, the coadministration of T and MMF did not sign ificantly alter T pharmacokinetics. (C) 2000 the American College of Clinic al Pharmacology.