Absorption characteristics of EC-MPS--an enteric-coated formulation of mycophenolic sodium.

Kliniken der Stadt Köln gGmbH, Clinic Merheim, Medical Clinic I, Cologne, Germany.
International journal of clinical pharmacology and therapeutics (Impact Factor: 1.2). 09/2006; 44(8):375-85. DOI: 10.5414/CPP44375
Source: PubMed

ABSTRACT Enteric-coated mycophenolate sodium is an advanced formulation delivering mycophenolic acid (MPA), designed to improve MPA-related upper gastrointestinal adverse events by delaying MPA release until the small intestine.
Two studies were undertaken to identify the absolute bioavailability and dose-proportionality of enteric-coated mycophenolate sodium in stable renal transplant patients receiving cyclosporine.
Study 1: The mean MPA AUC(0-t) was shown to be greater after MPA infusion than after oral enteric-coated mycophenolate sodium (42.1 vs. 28.9 microg x h/ml). Mean absolute bioavailability was 0.71 +/- 0.21 (SD). Study 2: The AUC(0-t) and C(max) for MPA were proportional to the dose of enteric-coated mycophenolate sodium, similarly mean AUC(0-infinity) and C(max) for MPA glucuronide were proportional to dose administered.
In patients receiving cyclosporine the absolute bioavailability of MPA provided by enteric-coated mycophenolate sodium is equivalent to that provided by mycophenolate mofetil when administered in combination with cyclosporine, and exhibits dose-proportionality. Enteric-coated mycophenolate sodium was well tolerated from 180 - 2,160 mg with no serious adverse events reported.

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    ABSTRACT: There are few pharmacokinetic data for enteric-coated mycophenolate sodium (EC-MPS) in Chinese kidney transplant recipients. Previously, we demonstrated that patients with 540 mg EC-MPS reached target exposure on day 4 after transplantation. The aim of this study was further to confirm that mycophenolic acid (MPA) delivery with a daily total dose 1080 mg EC-MPS is adequate during the early-phase posttransplantation and preliminarily assess the pharmacokinetics after a single dose and multiple doses of EC-MPS in Chinese live-donor kidney transplant recipients. Twelve patients (eight men and four women, mean age 41.3 ± 6.78 years) treated with EC-MPS, cyclosporine and corticosteroids were included in this study. Patients received a single oral dose of EC-MPS 540 mg, then 540 mg twice daily. MPA concentrations were measured by high-performance liquid chromatography. Twelve-hour pharmacokinetic profiles were obtained after the single oral dose and multiple doses on day 4 postoperation. The pharmacokinetic parameters were compared between a single dose and multiple doses. By using multiple stepwise regression analysis, we obtained two predictive equations of MPA systemic exposure. Bland-Altman analysis was developed to test agreement between the observed MPA area under the concentration-time curve (AUC) and the predicted MPA AUC. The mean (range) MPA AUC was 42 ± 14.67 (29.29-75.95) mg/l h after the first dose, and 44.72 ± 14.57 (32.06-80.79) mg/l h on day 4 after operation. MPA exposure provided by a single dose and multiple doses were similar (p > 0.05). The best equations obtained were the following: 20.003 + 1.181C6 h + 7.22C8 h (r = 0.936) and 17.023 + 3.11C1 h + 1.245 + 4.988C8 h (r = 0.964). These equation models showed an optimal agreement between the observed MPA AUC and the predicted MPA AUC. Lower dosing of EC-MPS, compared with the standard dose (720 mg twice daily), may provide enough MPA exposure for Chinese live-donor kidney transplant patients on day 4. Given that the MPA exposure by AUC correlates with the incidence of acute rejection episodes and transplant vasculopathy, the present findings may have clinical implications, and the optimum dose range of EC-MPS for patients in all ranges of body weight should also be determined.
    International journal of clinical practice. Supplement 04/2014; 68(181):31-7.
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