Mycophenolate mofetil pharmacokinetics

Zucker K, Rosen A, Tsaroucha A, et al. Augmentation of mycophenolate mofetil pharmacokinetics in renal transplant patients receiving Prograf and CellCept in combination therapy. Transplant Proc 1997 29(1—2) 334—336. 

Vidal E, Cantarell C, Capdevila L, Monforte V, Roman A, Pou L. Mycophenolate mofetil pharmacokinetics in transplant patients receiving cyclosporine or tacrolimus in combination therapy, Pharmacol Toxicol (2000) 87,182-4. 

Hale MD, Nicholls AJ, Bullingham RES, Hene R, Hoitsma A, Squifflet J-P, Weimar W, Vanrenterghem Y, Van de Woude FJ, Verpooten GA. (1998) The pharmacokinetic-pharmacodynamic relationship for mycophenolate mofetil in renal transplantation. Clin Pharmacol Ther 64 672-683. 

Budde K, Glander P, Grohmann J, Bauer S, Hambach P, Hepburn H, Mai I, Sandau K, Fischer W, Neumayer HH. (2004) Pharmacokinetic and pharmacodynamic comparison of mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS) in maintenance renal transplant patients with tacrolimus as basic immunosuppression (P736). Transplantation 78 459 60. 

Drug interactions In a randomized, double-blind study, Zenapax or placebo was added to an immunosuppressive regimen of cyclosporine, mycophenolate mofetil, and steroids to assess tolerability, pharmacokinetics, and drug interactions. The addition of Zenapax did not result in an increased incidence of adverse events or a change in the types of adverse events reported. The following medications have been administered in clinical trials with Zenapax with no incremental increase in adverse reactions cyclosporine, mycophenolate mofetil, ganciclovir, acyclovir, azathioprine, and corticosteroids. 

Mycophenolate mofetil (MMF) is converted to mycophenolic acid, the active form of the drug. The active product inhibits cytosine monophosphate dehydrogenase and, secondarily, inhibits T-cell lymphocyte proliferation downstream, it interferes with leukocyte adhesion to endothelial cells through inhibition of E-selectin, P-selectin, and intercellular adhesion molecule 1. MMF s pharmacokinetics and toxicities are discussed in Chapter 55. 

Fulton B, Markham A (1996) Mycophenolate mofetil. A review of its pharmacodynamic and pharmacokinetic properties and clinical efficacy in renal transplantation. Drugs 51 278-298. 

Bullingham RES, Nicholls AJ, Kamm BR. Clinical pharmacokinetics of mycophenolate mofetil. CUn Pharmacokinet 1998 34 429 55. 

Pescovitz MD, Conti D, Dunn J, et al. Intravenous mycophenolate mofetil Safety, tolerability, and pharmacokinetics. Clin Transplant 2000 14 179-188. 

Cox VC, Ensom MHH. Mycophenolate mofetil for solid organ transplantation Does the evidence support the need for clinical pharmacokinetic monitoring Ther Drug Monit 2003 25 137-157. 

Disposition and Pharmacokinetics Mycophenolate mofetil is rapidly and completely metabolized to MPA after oral or intravenous administration. MPA, in turn, is metabolized to the inactive glucuronide MPAG. The parent drug is cleared from the blood within a few minutes. The tj of MPA is 16 hours. Negligible (<1%) amounts of MPA are excreted in the urine. Most (87%) is excreted in the urine as MPAG. Plasma concentrations of MPA and MPAG are increased in patients with renal insufficiency. In early renal transplant patients (<40 days post-transplant), plasma concentrations of MPA after a single dose of mycophenolate mofetil are approximately half of those found in healthy volunteers or stable renal transplant patients. 

The concurrent use of aciclovir or ganciclovir and mycophenolate mofetil does not appear to significantly affect the pharmacokinetics of either drug, but the manufacturers recommend care in renal impairment. There are reports of neutropenia in patients taking mycophenolate with valaciclovir or ganciclovir. 

S3mtex. A single-dose, pharmacokinetic drug interaction study of oral mycophenolate mofetil and oral acyclovir in normal subjects. Data on file, 1994. 

Gimenez F, Foeillet E, Bourdon O, Weller S, Garret C, Bidault R, Singlas E. Evaluation of pharmacokinetic interactions after oral administration of mycophenolate mofetil and valaciclovir or aciclovir to healftiy subjects. Clin Pharmacokinet (2004) 43, 685-92. 

Wolfe EJ, Mathur V, Tomlanovich S, Jung D, Wong R, Griffy K, Aweeka FT. Pharmacokinetics of mycophenolate mofetil and intravenous ganciclovir alone and in combination in renal transplant recipients. Pharmacotherapy 99T) 17, 591-8. 

Bullingham R, Shah J, Goldblum R, Schiff M. Effects of food and antacid on the pharmacokinetics of single doses of mycophenolate mofetil in rheumatoid arthritis patients, BrJ Clin Pharmacol (1996) 41, 513-16. 

The addition of mycophenolate mofetil to ciclosporin has been found to reduce the incidence of rejection episodes in kidney transplant patients and it is licensed for combined use. From the studies above, ciclosporin appears to reduce the levels of the active metabolite, mycophenolic acid, and increase the levels of the glucuronide metabolite (which is associated with mycophenolate adverse effects). The UK manufacturers point out that as efficacy studies were conducted in patients using ciclosporin, mycophenolate and corticosteroids, the finding that ciclosporin reduces the mycophenolic acid AUC by 19% to 38% does not affect the recommended dose requirements. They also state that ciclosporin pharmacokinetics are not affected by mycophenolate. However, this is in contrast to the studies... 

Pirsch J, Bekersky I, Vincent F, BosweU G, Woodle ES, Alak A, Kruelle M, PassN, Facklam D, Meldci Q. Coadministration of tacrolimus and mycophenolate mofetil in stable kidney ttansplant patients pharmacokinetics and tolerability. JC/mPhamaco/(2000) 40, 527-32. 

A study in patients with rheumatoid arthritis found that the combination of methotrexate and mycophenolate mofetil was well tolerated and there were no pharmacokinetic interactions. There would appear to be no need for dose adjustments if both drugs are given for rheumatoid arthritis. 

Yocum D, Kremer J, Blackburn W, Caldwell J, Furst D, Nunez M, Zuzga J, Zeig S, Gutierrez M, Merrill J, Dumont E, B Leishman. Cellcept (mycophenolate mofetil - MMF) and methotrexate (MTX) safety and pharmacokinetic (PK) interaction study in rheumatoid arthritis patients./irt/rntisR/rewm (1999) 42 (9 Suppl), S83. 

Pieper A-K, Buhle F, Bauer S, Mai I, Budde K, Haf ier D, Neumayer H-H, Querfeld U. The effect of sevelamer on pharmacokinetics of cyclosporin A and mycophenolate-mofetil after renal tiansplantation. NephrolDial Transplant(2004) 19, 2630-3. 

Drug-drug interactions Mycophenolate mofetil In a pharmacokinetic study of telmisartan, valsartan, and candesartan in combination with mycophenolate mofetil in renal transplant patients, telmisartan increased the elimination of mycophenolic acid there was no interaction with valsartan or candesartan [57 ]. It was suggested that this was due to activation by... 

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