In Vivo Higher Glucuronidation of Mycophenolic Acid in Male Than in Female Recipients of a Cadaveric Kidney Allograft and Under Immunosuppressive Therapy With Mycophenolate Mofetil
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Bibliographic record
Abstract
Mycophenolate mofetil (MMF), an immunosuppressant drug used in organ transplantation to prevent rejection, is being used increasingly in association with cyclosporine and tacrolimus. Mycophenolic acid (MPA) is primarily metabolized in the liver to its 7-O-glucuronide (MPAG) derivative. The concentrations of MPAG in serum are many times the concentrations of MPA. Although MPAG has not shown immunosuppressant activity, it was postulated that it could displace MPA from its binding sites on albumin and hence increase the biologic effects of MPA. This effect could be important for patients with acute renal failure; under this condition, MPAG was shown to accumulate. The goal of this study was to document the MPAG/MPA concentration ratio in 100 renal transplant patients under a mixed immunosuppressive therapy. Further, the study addressed the question of whether MPAG can displace MPA in vivo from bound albumin in a representative renal transplant patient population under immunosuppressive therapy. Levels of MPAG and MPA were measured by high-performance liquid chromatography. The distribution of the ratios was not parametric as it tailed toward elevated values. After a square root transformation of the data, parametric analysis was possible. The average MPAG/MPA ratio was 15.0 +/- 2.2 for men versus 7.7 +/- 0.9 for women. Men treated with MMF and tacrolimus showed a lower ratio than patients treated with MMF and cyclosporine, confirming that tacrolimus inhibits glucuronidation of MPA. Further, it was determined that at physiologic concentrations, MPAG does not increase the amount of free MPA. Because MPAG can favor the elimination of MPA, it can be concluded that gender differences and cotreatment with tacrolimus must be taken into consideration when MMF is being administered.
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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 it