A Comparison of Short-Term Exposure of Once-Daily Extended Release Tacrolimus and Twice-Daily Cyclosporine on Renal Function in Healthy Volunteers
Bibliographic record
Abstract
BACKGROUND: Calcineurin inhibitor nephrotoxicity remains an issue for recipients of solid organ transplants. After cyclosporine A (CsA) microemulsion administration, effective renal plasma flow (ERPF) and glomerular filtration rate(GFR) are decreased coincident with the maximal concentration (Cmax) of CsA. The pharmacokinetic (PK) profile of the once-daily formulation of tacrolimus extended release (Tac ER) includes an equivalent AUCPK 0-24 hr and a lower Cmax versus twice-daily Tac immediate release. METHODS: Eighteen healthy subjects were allocated once-daily Tac ER and twice-daily CsA in a prospective, randomized,open-label, two-period, two-sequence single crossover study. CsA was targeted to C2 of 700 to 1400 ng/mL, and Tac ER was targeted to C0 of 5 to 10 ng/mL. Pharmacodynamic (PD) assessments were conducted preexposure, and PD and PK were assessed during a 6-hr postdose period after 10-day exposure. RESULTS: The achieved mean C(o) Tac and CsA were 6.4 +/- 1.16 and 201 +/- 57 ng/mL, respectively. At Cmax, the change in ERPF was +30 +/- 127 vs. -70 +/- 96 mL/min/1.73 m2 relative to baseline for Tac ER and CsA (P=0.0085). The ERPF and GFR AUC (PD 0-6) hr were 3645 +/- 887 vs. 3210 +/- 582 mL/1.73 m2 (P=0.027) and 604 +/- 98 vs. 543+/- 79 mL/1.73 m2(P=0.023) for Tac ER versus CsA, respectively. Both systolic and diastolic blood pressures were significantly greater with exposure to CsA compared with Tac ER. CONCLUSIONS: Acute reductions in ERPF and GFR are attenuated with Tac ER compared with CsA and may correlate with the differing PK profiles of these calcineurin inhibitors.
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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".