Pharmacokinetic and Pharmacodynamic Comparison of Enteric-Coated Mycophenolate Sodium and Mycophenolate Mofetil in Maintenance Renal Transplant Patients

Abstract

and predose MPA levels (geometric mean 2.10; 90% CI: 1.51-2.91) were higher and more variable, not fulfilling bioequivalence criteria. IMPDH activity inversely followed MPA concentrations and was inhibited to a similar degree (approximately 85%) by both formulations. The calculated value for 50% IMPDH inhibition was identical for both drugs. In conclusion, equimolar doses of EC-MPS and MMF produce equivalent MPA exposure, while the delayed release formulation of EC-MPS exhibits more variable predose levels and T max . Overall, IMPDH activity reflected MPA pharmacokinetics.

Consensus Report on Therapeutic Drug Monitoring of Mycophenolic Acid in Solid Organ Transplantation

“…For MPA predose trough concentrations, the mean intraindividual coefficient of variation (CV) ranges from 36 to 62%, whereas a mean intraindividual CV of 30 to 47% (range 18 to 80%) has been described for MPA AUC 0 to 12 hours (27). For the enteric-coated MPA formulation, intrasubject CVs for exposure parameters (except maximum concentration) are comparable (28). The relatively high within-subject variability of MPA exposure is an important limitation for the development of useful TDM strategies.…”

“…Regarding MPA pharmacokinetics and dynamics, it has been demonstrated that administration of nearly equimolar dosage of EC-MPS and MMF (720 and 1000 mg, respectively) results in a bioequivalent MPA full-dose interval AUC, similar exposure to MPAG and AcMPAG, and similar inosine monophosphate dehydrogenase (IMPDH) inhibition (2,28,29). MPA absorption from EC-MPS is delayed, resulting in a delayed enterohepatic recirculation and subsequently higher and more variable MPA 12-hour trough concentrations and tmax (time to reach maximum plasma concentrations) values (28-30); therefore, MPA trough level monitoring cannot be used as a guide to monitor MPA exposure in patients who are given EC-MPS (r 2 ϭ 0.02 for correlation between trough level and dose-interval AUC for EC-MPS and 0.48 for MMF respectively) (30).…”

Pharmacokinetics of Mycophenolate Sodium and Comparison with the Mofetil Formulation in Stable Kidney Transplant Recipients

“…Only a few studies (7)(8)(9)(10)(11)(12) have compared the pharmacokinetics of MPA in patients who were given EC-MPS or MMF. It was shown that both formulations provide equivalent MPA exposure in heart (10) or kidney (9,11,12) transplant recipients; however, heterogeneity in the study population regarding the time after transplantation (9,11,12)-a condition that is known to affect MPA pharmacokinetics (13)-and limited MPA pharmacokinetic data in some instances did preclude any definite conclusion about comparability of the two MPA formulations.…”

Mycophenolic acid agents: is enteric coating the answer?

“…Consistent with characteristics of the entericcoated formulation, EC-MPS demonstrated delayed t max compared with MMF. 14,15 And, as would be expected, the 11,13 MPA binds to plasma albumin in a concentration-dependent manner, the plasma concentration of unbound MPA increasing as the dose increases. 16 The protein binding of MPA's main metabolite, mycophenolic acid glucuronide (MPAG), is 82%.…”