Cyclosporine disposition in pediatric hematopoietic stem cell transplantation patients after IV and oral administration
Bibliographic record
Abstract
This study describes the disposition of cyclosporine in 24 children undergoing HSCT after IV administration and oral administration of 2 different formulations: Neoral® and Sandimmune®. Whole-blood samples for cyclosporine measurement were obtained after the first IV cyclosporine dose on day −1 and after the morning dose on each of the first 2 days of oral cyclosporine administration. Neoral® was given on the first day of oral cyclosporine administration, and a single dose of Sandimmune® was given in the morning of the second day. Oral cyclosporine doses were identical and were given on an empty stomach. Cyclosporine concentration-time data were analyzed by noncompartmental methods. A total of 24 children completed the study. After IV administration of 1.5± 0.07 mg/kg, the mean cyclosporine maximum concentration (Cmax), volume of distribution at steady state, elimination half-life, clearance, and area under the concentration-versus-time curve (AUC) were 1103.4± 787.71 μg/L, 2.6± 1.52 L/kg, 4.2± 2.49 hours, 0.56± 0.255 L/hr/kg, and 2852± 1198 μg· hr· L−1, respectively. Children took their first oral cyclosporine dose on average 29.4± 6.88 days after their first IV dose. The mean Cmax observed after Neoral® administration was significantly higher than after Sandimmune® administration (595 ±349.7 vs 486± 363.0 μg/L; P= .043), as was AUC 0–12 hr (3432± 1563 vs 3144± 1780 μg· hr· L−1; P= .022). There was no difference in time to reach Cmax (tmax) between the formulations. The coefficients of variation in Cmax, tmax, and AUC were all lower with Neoral® than with Sandimmune®, but remained substantial. The cyclosporine concentration at hour 4 after oral Neoral® and Sandimmune® administration exhibited the strongest correlation with AUC0–12 hr. However, unlike Sandimmune®, the trough cyclosporine concentration after Neoral® administration showed the weakest relationship with AUC (Spearman’s ρ coefficient= 0.568; P= .027). In children undergoing HSCT, cyclosporine absorption is lower than that usually seen in children who have undergone solid organ transplantations. The relationship between cyclosporine concentrations during the dosing interval and AUC differs depending on the oral formulation administered. Thus, Neoral® dose adjustment based on trough concentration may not be appropriate. The link between pharmacokinetic parameters and clinical outcomes such as GvHD must be studied further.
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 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 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".