Intravenous mycophenolate mofetil: safety, tolerability, and pharmacokinetics.

An intravenous (i.v.) formulation of mycophenolate mofetil (MMF; CellCept, Roche Pharmaceuticals, Inc., Palo Alto, CA) that will enable its administration to patients unable to tolerate oral medication is available. Two separate studies, an open-labeled pharmacokinetic (PK) study and a double-blind safety study, were performed. Within 24 h after transplant, 153 (safety study) and 45 (PK study) first or second renal transplant recipients were started on i.v. MMF 1 g Q12h or placebo (used in the safety study only, 2:1 MMF:placebo), given over 2 h via a dedicated peripheral venous catheter. In the safety study, per os (p.o.) MMF (1g Q12h) or placebo was administered, starting within 72 h after transplant, whereas in the PK study, p.o. MMF was started on the evening of day 5. Sequential blood samples obtained on study days 5 (i.v. MMF) and 6 (p.o. MMF) before and up to 12 h after the AM dose were analyzed for mycophenolic acid (MPA) and MPA glucuronide (MPAG) concentrations by high-performance liquid chromatography. The area under the concentration curve (AUC) was calculated using the linear trapezoidal rule. The MPA AUC(0-12) was higher for i.v. MMF than p.o. MMF (40.8 +/- 11.4 microg x h/ mL vs. 32.9 +/- 15, p < 0.001). There were no other significant PK differences for plasma MPA or MPAG. In the safety study (n = 98 i.v. MMF vs. n = 55 placebo), 11 patients (11%, i.v. MMF) and 4 patients (7%, placebo) discontinued their use of the drug because of an adverse event (AE). Overall, AEs were similar between i.v. MMF and placebo. Injection site phlebitis (4%) and thrombosis (4%) were observed only with i.v. MMF. MMF i.v. 1 g twice daily (b.i.d.) should provide efficacy at least equivalent to p.o. MMF without increased toxicity, and it provides an acceptable alternative dose form in the immediate period after transplant.

RCT Entities:   Population Interventions Outcomes