Pharmacokinetics and variability of mycophenolic acid from enteric‐coated mycophenolate sodium compared with mycophenolate mofetil in <i>de novo</i> heart transplant recipients
Bibliographic record
Abstract
Sequential pharmacokinetic assessments were performed at five centers within the context of a multicenter, single-blind, randomized clinical trial comparing the efficacy and safety of enteric-coated mycophenolate sodium (EC-MPS, myfortic) and mycophenolate mofetil (MMF, CellCept) in de novo heart transplant recipients. Patients were randomized to either EC-MPS 1080 mg bid or MMF 1500 mg bid, as part of a triple immunosuppressive therapy including cyclosporine microemulsion. Steady-state pharmacokinetic profiles of mycophenolic acid (MPA) and its inactive phenolic glucuronide (MPAG) were assessed at weeks 2, 12, and 52. Pharmacokinetic parameters were evaluated in 32 patients (17 on EC-MPS and 15 on MMF). Dose-normalized peak (C(max,ss)) and area under the curve (AUC(tau,ss)) of MPA and MPAG increased between week 2 and week 12 assessments for both treatments. Comparisons between EC-MPS and MMF showed no statistically significant differences in MPA and MPAG AUC(tau,ss), C(max,ss), and trough (C(min,ss)) values (p-values ranged from 0.225 to 0.990). Consistent with the delayed release characteristics of EC-MPS, C(max,ss) occurred approximately one hour later compared with MMF. Inter-subject coefficients of variation (%CV) for MPA pharmacokinetic parameters of both EC-MPS and MMF were high (37-72% for AUC(tau,ss) at weeks 2 and 12). Also within patients, the pharmacokinetics of MPA varied considerably. Specifically, intra-subject %CVs for MPA AUC(tau,ss), C(max,ss), and C(min,ss) were 28%, 63%, and 34% with EC-MPS and 54%, 139%, and 41% with MMF respectively. These results indicate that a dose of EC-MPS 1080 mg bid in combination with cyclosporine provides adequate systemic MPA exposure in de novo heart transplant patients, comparable with MMF 1500 mg bid. Overall, there is a large inter- and intra-subject variability in MPA pharmacokinetic parameters with both treatments.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".