Pharmacocinétique des médicaments en insuffisance rénale : nouveautés
Bibliographic record
Abstract
La prévalence et l’incidence de l’insuffisance rénale chronique (IRC) ne cessent d’augmenter depuis les deux dernières décennies, notamment en raison d’une augmentation importante des cas de diabète, d’hypertension et d’obésité, principaux facteurs de risque de l’insuffisance rénale. L’IRC affecte l’élimination de médicaments non éliminés par voie rénale pouvant ainsi conduire à une toxicité involontaire ou à un faible effet thérapeutique malgré l’ajustement de la dose en fonction du débit de filtration glomérulaire. L’altération de la pharmacocinétique en IRC peut s’expliquer par la modulation des enzymes du métabolisme (cytochrome P450, phase II) et des transporteurs de médicaments dans divers organes (intestins, foie, reins et cerveau), où les toxines urémiques, les cytokines inflammatoires et l’hormone parathyroïdienne, facteurs communs présents en IRC, peuvent être tenus responsables. Cet article de revue donne un résumé complet des dernières études précliniques, cliniques et directives de la Food and Drug Administration (FDA) et permet une compréhension actuelle de l’absorption du médicament, de sa distribution, de son métabolisme et de son excrétion en IRC. The prevalence and incidence of chronic kidney disease (CKD) has steadily increased over the past two decades attributed to an important raise of cases of diabetes, hypertension and obesity, leading risk factors of renal failure. CKD is known to impair drug disposition of non-renally eliminated medications that may lead to unintended toxicity or lower therapeutic effect despite dose adjustment according to glomerular filtration rate (GFR). Modulation of metabolism enzymes (cytochrome P450, phase II) and drug transporters in various organs (intestines, liver, kidneys and brain) are being held responsible for altered pharmacokinetics where uremic toxins, inflammatory cytokines and parathyroid hormone, common factors present in CKD, may be considered possible culprits. This review gives a thorough summary of the recent preclinical, clinical studies and Food and Drug Administration (FDA) guidelines and allows a current understanding of drug absorption, distribution, metabolism and excretion in CKD.
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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 | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.006 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.003 | 0.005 |
| Insufficient payload (model declined to judge) | 0.002 | 0.003 |
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; both teacher heads agree on what is shown here.
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".