Pharmacokinetics of Mycophenolic Acid and its Phenolic-Glucuronide and Acyl Glucuronide Metabolites in Stable Thoracic Transplant Recipients
Bibliographic record
Abstract
Mycophenolate mofetil is an immunosuppressant commonly used in solid organ transplantation. Its active metabolite, mycophenolic acid (MPA), is metabolized to the inactive 7-O-mycophenolic acid glucuronide (MPAG) and the active acyl glucuronide (AcMPAG). Most pharmacokinetic (PK) studies have been focused on MPA, but not its metabolites, in kidney transplant recipients. Pharmacokinetic studies of MPA and its metabolites in thoracic transplant recipients are scarce. Because neither the heart nor lung is involved in MPA metabolism or excretion, the thoracic transplant population may exhibit unique PKs. This open-label study aimed to characterize and compare PKs of MPA and its metabolites in stable lung or heart transplant recipients. Fifty thoracic (27 lung, 23 heart) transplant recipients were recruited. Subjects were also taking cyclosporine (11 lung, 14 heart) or tacrolimus (16 lung, nine heart), and prednisone (27 lung, one heart). Blood samples were obtained at 0, 20, 40, 60, and 90 minutes and 2, 4, 6, 8, 10, and 12 hours postdose. Plasma was used for drug level analysis (MPA, MPAG, and AcMPAG) by a high-performance liquid chromatography-ultraviolet detection method; in a subset of subjects, free MPA concentrations were also determined. Conventional PK parameters (dose-normalized) were determined by noncompartmental methods. There was wide interpatient variability of MPA, MPAG, and AcMPAG PKs with coefficients of variation exceeding 70% for most PK parameters measured. Other findings (P < 0.05) included: lower MPA area under the curve, maximum concentration, and minimum concentration; higher apparent clearance and MPAG/MPA metabolic ratio in the lung versus heart transplant group; lower MPA area under the curve and minimum concentration, and higher apparent clearance and MPAG/MPA metabolic ratio in lung transplant recipients concurrently taking cyclosporine versus tacrolimus; and lower minimum concentration in heart transplant recipients taking cyclosporine versus tacrolimus. Despite large interpatient variability in the PKs of MPA, MPAG, and AcMPAG among thoracic transplant recipients, there appear to be significant differences between lung and heart patients, which warrant further study.
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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) | 0.000 | 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".