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

J Pirsch, I Bekersky, F Vincenti… - The Journal of …, 2000 - Wiley Online Library
J Pirsch, I Bekersky, F Vincenti, G Boswell, ES Woodle, A Alak, M Kruelle, N Fass, D Facklam…
The Journal of Clinical Pharmacology, 2000Wiley Online Library
The tolerance and pharmacokinetics (PK) of tacrolimus (T) by the addition of mycophenolate
mofetil (MMF) in stable kidney transplant patients (6/group) on long‐term tacrolimus‐based
therapy were investigated. Patients received combination T and MMF therapy at three MMF
doses: 1, 1.5, and 2 g/day administered 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 administration …
The tolerance and pharmacokinetics (PK) of tacrolimus (T) by the addition of mycophenolate mofetil (MMF) in stable kidney transplant patients (6/group) on long‐term tacrolimus‐based therapy were investigated. Patients received combination T and MMF therapy at three MMF doses: 1, 1.5, and 2 g/day administered 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 administration. Tolerance was monitored through 3 months. The intra‐ and intergroup PK of T were variable. The mean AUC0–12 of T for each group was increased after 2 weeks of concomitant MMF administration, but the increase was not statistically significant. Both drugs were well tolerated. Gastrointestinal events were of interest as such have been attributed to both T and MMF. Events reported were diarrhea, nausea, dyspepsia, and vomiting. Other common adverse events were headache, hypomagnesemia, 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 significantly alter T pharmacokinetics.
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