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 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.
Pirsch
J
J
University of Wisconsin, Madison, USA.
Bekersky
I
I
Vincenti
F
F
Boswell
G
G
Woodle
E S
ES
Alak
A
A
Kruelle
M
M
Fass
N
N
Facklam
D
D
Mekki
Q
Q
D000328:Adult; D019540:Area Under Curve; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004415:Dyspepsia / Q000139:chemically induced; D005260:Female; D005965:Glucuronates / Q000097:blood; D020719:Glucuronides; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D009325:Nausea / Q000139:chemically induced; D011355:Prodrugs / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D016559:Tacrolimus / Q000009:adverse effects / Q000493:pharmacokinetics*; D014839:Vomiting / Q000139:chemically induced
D005965:Glucuronates; D020719:Glucuronides; D007166:Immunosuppressive Agents; D011355:Prodrugs; C113145:mycophenolic acid glucuronide; D009173:Mycophenolic Acid; D016559:Tacrolimus