Ganciclovir Pharmacokinetic Parameters Do Not Change When Extending Valganciclovir Cytomegalovirus Prophylaxis From 100 to 200 Days
Bibliographic record
Abstract
BACKGROUND: A 3-month course of prophylaxis is usually recommended for cytomegalovirus (CMV) D+/R- renal transplant recipients. Based on recent data, up to 6 months of prophylaxis may be used. A subanalysis was performed to evaluate the pharmacokinetics of ganciclovir after valganciclovir administration and to perform an exploratory pharmacokinetic/pharmacodynamic analysis. METHODS: In Improved Protection Against Cytomegalovirus in Transplant, a phase III, randomized, double blind, placebo-controlled, multicenter study, 318 CMV D+/R- kidney transplant recipients received valganciclovir prophylaxis (900 mg once daily) for 200 or 100 days. A population pharmacokinetic analysis was conducted on a subgroup of patients (n=120). The relationships between ganciclovir exposure (AUC0-24 hr) and clinical outcomes were explored. RESULTS: The final population parameter estimates (95% confidence interval) were as follows: apparent clearance of ganciclovir, 12 L/hr (11.3-12.7 L/hr); volume of distribution, 18.5 L (14.4-22.6 L); and peripheral volume, 44.4 L (40.2-48.6 L). No differences were apparent between the two treatment groups and these estimates. These results are consistent with previously published pharmacokinetic models. There were no direct correlations between the likelihood of developing hematologic adverse events and ganciclovir exposure at the time of the event. The incidence of CMV disease was not correlated with ganciclovir exposure. CONCLUSION: The pharmacokinetics of ganciclovir were similar between the two dosing groups (100 vs. 200 days), with the majority of patients achieving an area under the concentration time curve in the target therapeutic range (40-60 μg hr/mL). The fact that the majority of patients were within the target therapeutic range and the absence of a control arm (no treatment) precluded any attempt to validate a correlation with clinical parameters (i.e., CMV disease).
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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 | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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".