FACTORS AFFECTING THE DISPOSITION OF DIFILUNISAL AND ITS METABOLITES.
Notice bibliographique
Résumé
Diflunisal is a nonsteroidal anti-inflammatory drug used in the treatment of arthritis and musculoskeletal pain. Diflunisal is mainly eliminated by metabolism. Non-linear elimination and saturable plasma protein binding of diflunisal in humans is well recognized. The non-linear elimination of diflunisal is a result of saturation of the formation of diflunisal acyl glucuronide (DG) following administration of increasing single doses (100 - 1000 mg) and the saturation of both acyl and phenolic glucuronide (DG) pathways following multiple doses (250 mg to 500 mg twice daily).\n\nThe objective of this study was to examine the effect of physiologic (male vs females), pathologic (cirrhosis) and pharmacologic (smoking, OCS and paid) factors, known to have an impact on conjugation, on the pharmacokinetics of diflunisal The studies were designed to examine the effect of these factors on the total clearance of difliaiisal and to determine if there are any differential effects on specific metabolic pathways.\n\nHigh performance liquid chromatography (HPLC) assays were developed to analyze diflunisal and its conjugates in urine and plasma. The plasma protein binding of diflunisal was determined both in vitro and ex vivo using equilibrium dialysis.\n\nIn an attempt to improve the chromatographic properties of the diflunisal sulphate conjugate (DS), the analytical HPIC assay of Loewen et al (1989) was modified by adding anhydrous Na2SO4 (0.0]M) to the aqueous nubile phase. With Na2SO4 in the mobile phase, a new peak appeared on the chromatogram of urine samples. Although the material could be isolated, it was too unstable to identify by mass spectrometry The unidentified material was isolated and hydrolyzed by ether extraction. The hydrolysis product was identified by mass spectrometry and NMR spectroscopy as 3 hydroxy diflunisal. The unidentified peak seen on chromatography of urine samples is thought to be a conjugate of this 3 hydroxy metabolite. The metabolic importance of the 3-hydroxy metabolite of diflunisal has not been determined, although smoking may induce this metabolic pathway.\n\nThe effect of cirrhosis on the disposition of diflunisal was examined in 5 cirrhosis patients and 5 sex and age matched controls. The apparent volume of distribution, the elimination half-life and total clearance of diflunisal were unaltered by cirrhosis. The intrinsic ability of the liver to glucuronidate diflunisal seemed to be reduced in cirrhosis, whereas sulphation remained unchanged. The percent unbound of diflunisal was increased in cirrhosis (0.073 to 0.121%). The reduction in glucuronidation capacity appeared to be offset by an increase in the free fraction of diflunisal in cirrhosis, resulting in no overall change in clearance.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».