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Coadministration of Tacrolimus and Mycophenolate Mofetil in Stable Kidney Transplant Patients: Pharmacokinetics and Tolerability
Author(s) -
Pirsch John,
Bekersky Ihor,
Vincenti Flavio,
Boswell Garry,
Woodle E. Steve,
Alak Ala,
Kruelle Margaret,
Fass Nancy,
Facklam David,
Mekki Qais
Publication year - 2000
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912700022009143
Subject(s) - mycophenolic acid , medicine , tacrolimus , pharmacokinetics , concomitant , tolerability , adverse effect , pharmacology , mycophenolate , nausea , gastroenterology , transplantation
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 AUC 0–12 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.