Pharmacokinetics and Protein Binding of Mycophenolic Acid in Stable Lung Transplant Recipients
Bibliographic record
Abstract
Mycophenolate mofetil (MMF) use is increasing in solid organ transplantation. Mycophenolic acid (MPA), the active metabolite of MMF, is highly protein bound and only free MPA is pharmacologically active. The average MPA free fraction in healthy adult individuals, stable renal transplant recipients, and heart transplant recipients is approximately 2 to 3%. However, no data are currently available on MPA protein binding in stable lung transplant recipients and little is known regarding MPA's pharmacokinetic characteristics after lung transplantation. The purpose of this study was to characterize the pharmacokinetic profile and protein binding of MPA in this patient population. Seven patients were entered into the study. On administration of a steady-state morning MMF dose, blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 8, 9, 10, and 12 hours post-dose. Total MPA concentrations were measured by a validated HPLC method with UV detection and followed by ultrafiltration of pooled samples for free MPA concentrations. Area under the curve (AUC), peak concentration (Cmax), time to peak concentration (Tmax), trough concentration (Cmin), free fraction (f), and free MPA AUC were calculated by traditional pharmacokinetic methods. Patient characteristics included; 3 males and 4 females, an average of 4.4 years post-lung transplant (range, 0.3-11.5 yr), mean (+/- SD) age of 50 +/- 10 years and weight 69 +/- 20 kg. Mean albumin concentration was 37 +/- 3 g/L and serum creatinine was 142 +/- 49 micromol/L. All patients were on cyclosporine and prednisone. MMF dosage ranged from 1 to 3 g daily (35.5 +/- 14.1 mg/kg/d; range, 15.2-60.0 mg/kg/d). Mean (+/- SD) AUC was 45.78 +/- 18.35 microg.h/mL (range, 16.56-74.22 microg.h/mL), Cmax was 17.37 +/- 7.69 microg/mL (range, 4.92-26.63 microg/mL), Tmax was 1.2 +/- 0.4 hours (range, 1.0-2.0 h), Cmin was 3.12 +/- 1.41 microg/mL (range, 1.47-4.82 microg/mL), f was 2.90 +/- 0.56% (range, 2.00-3.40%), and free MPA AUC was 1.29 +/- 0.50 microg.h/mL (range, 0.54-1.88 microg.h/mL). This is the first study to determine these pharmacokinetic characteristics of MPA in the lung transplant population. Further studies should focus on identification of MMF dosing strategies that optimize immunosuppressive efficacy and minimize toxicity in lung allograft recipients.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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".