Pharmacokinetics of Mycophenolic Acid and Its Glucuronidated Metabolites in Stable Lung Transplant Recipients
Bibliographic record
Abstract
BACKGROUND: Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil, an immunosuppressive agent commonly used in solid organ transplantation. MPA is metabolized to the inactive metabolite 7-O-mycophenolic acid glucuronide (MPAG) and the active metabolite acyl glucuronide (AcMPAG). Pharmacokinetic profiling of MPA by determining AUC is a tool for determining drug exposure. Many studies, conducted primarily in kidney and some heart and liver transplant recipients, have shown wide interpatient variability in MPA's pharmacokinetic parameters. There have been few studies in the lung transplant group and, even though the lung is not involved in drug elimination, these patients may have different MPA pharmacokinetic characteristics. OBJECTIVE: To characterize the pharmacokinetic parameters and metabolic ratios of MPA in stable adult lung transplant recipients. METHODS: In an open-label manner, lung transplant recipients were recruited. Blood samples were obtained at 0, 0.3, 0.6, 1, 1.5, 2, 4, 6, 8, 10, and 12 hours postdose. Plasma was separated and acidified for drug concentration analysis (MPA, MPAG, AcMPAG) by an HPLC-ultraviolet detection method. Conventional pharmacokinetic parameters were determined via noncompartmental methods. RESULTS: There was large interpatient variability in all pharmacokinetic parameters of MPA, MPAG, and AcMPAG. Similar variability was observed after stratifying patients into concomitant medication groups: cyclosporine and tacrolimus. There was a trend for the tacrolimus group to have a higher dose-normalized AUC, higher AUC, lower apparent clearance, and lower AUC ratio of AcMPAG/MPA compared with the cyclosporine group. In addition, the cyclosporine group had a lower minimum concentration and higher AUC ratio of MPAG/MPA than did the tacrolimus group (p < 0.05). CONCLUSIONS: Because of the large interpatient variability in the pharmacokinetic parameters of MPA, MPAG, and AcMPAG, therapeutic drug monitoring of MPA and its metabolites in lung transplant recipients may be beneficial.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".