Randomized calcineurin inhibitor cross over study to measure the pharmacokinetics of co-administered enteric-coated mycophenolate sodium.
Enteric-coated mycophenolate sodium (EC-MPS) (myfortic) is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal adverse events by delaying the release of MPA until the small intestine. A randomized, calcineurin inhibitor crossover, steady-state pharmacokinetic study in stable renal transplant patients receiving EC-MPS demonstrated increased MPA exposure of 19% higher, MPA C(max,ss) 19% lower and MPA C(min,ss) approximately twofold higher with tacrolimus, than cyclosporine microemulsion. No study drug-related adverse events were recorded, but mean blood glucose concentration was higher in patients receiving tacrolimus (p = 0.031). The dose changes in relation to MPA exposure in patients is dependent on the clinical situation and may not always be warranted. These observations should be taken into consideration when switching from one calcineurin inhibitor to another, but the final dosage should be based on both this pharmacokinetic data and the clinical situation.
Kaplan
Bruce
B
Division of Nephrology, Department of Medicine, University of Florida College of Medicine, Gainesville, FL 32610-0224, USA. kaplab@medicine.ufl.edu
Meier-Kriesche
Herwig-Ulf
HU
Minnick
Paula
P
Bastien
Marie-Claude
MC
Sechaud
Romain
R
Yeh
Ching-Ming
CM
Balez
Sebastien
S
Picard
Franck
F
Schmouder
Robert
R
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D065095:Calcineurin Inhibitors; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000493:pharmacokinetics; D004655:Emulsions; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D012964:Sodium / Q000008:administration & dosage; D013608:Tablets, Enteric-Coated; D016559:Tacrolimus / Q000493:pharmacokinetics
D001786:Blood Glucose; D065095:Calcineurin Inhibitors; D004655:Emulsions; D004791:Enzyme Inhibitors; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine; D012964:Sodium; D009173:Mycophenolic Acid; D016559:Tacrolimus