Pharmacokinetics, Tolerability, and Safety of Intranasal Administration of Reformulated OxyContin® Tablets Compared with Original OxyContin® Tablets in Healthy Adults
Notice bibliographique
Résumé
BACKGROUND AND OBJECTIVE: Reformulated OxyContin(®) (oxycodone-HCl controlled release) tablets (ORF) became available in the United States in August 2010. The original formulation of OxyContin(®) (oxycodone-HCl controlled release) tablets (OC) used a delivery system that did not provide inherent resistance to crushing and dissolving. The objective of this study was to compare the pharmacokinetics, tolerability, and safety of finely crushed ORF tablets, coarsely crushed ORF tablets, and finely crushed OC tablets. METHODS: This randomized, single-blind, single-dose, single-center, six-sequence, triple-treatment, triple-period crossover study enrolled eligible healthy adults (aged 18-55 years inclusive). The study evaluated the pharmacokinetics, tolerability, and safety of intranasally administered ORF, both finely crushed and coarsely crushed, as well as finely crushed OC tablets. Plasma oxycodone concentrations were quantified and analyzed to determine the maximum observed plasma concentration (C max), time to maximum plasma concentration (t max), area under the plasma concentration-time curve from hour 0 to the last measurable plasma concentration (AUC(last)), and area under the plasma concentration-time curve extrapolated to infinity (AUC(∞)). The abuse quotient (AQ), calculated as C(max)/t(max), served as an index of the average rate of increase in drug concentration from dosing to t max. Intranasal tolerability rating scales (discomfort, itching, burning, pain, runny nose, and stuffiness) and intranasal endoscopy were conducted. Safety assessments included adverse events, vital signs, pulse oximetry (SpO2), and electrocardiograms. RESULTS: Of 83 subjects screened and enrolled, 30 were randomized to period 1, with 1 subject subsequently discontinuing due to the subject's choice. Mean C max values for finely crushed ORF (17.1 ng/mL) and coarsely crushed ORF (15.5 ng/mL) were lower than that for finely crushed OC (22.2 ng/mL). Median t max for finely crushed OC (1.0 h) was shorter than that for either finely crushed ORF (2.0 h) or coarsely crushed ORF (3.0 h). Mean AQ values were approximately 66 and 80 % lower, respectively, for finely crushed ORF and coarsely crushed ORF than that for finely crushed OC. Finely crushed ORF, coarsely crushed ORF, and finely crushed OC demonstrated similar total oxycodone exposures (AUC(∞)). Insufflation of ORF produced greater nasal discomfort and stuffiness than finely crushed OC, although the latter produced higher runny nose scores. No significant difference was found in other nasal tolerability measures. The overall safety profile was as expected following opioid administration in healthy subjects. CONCLUSIONS: In contrast to OC, both finely and coarsely crushed ORF retained some control of oxycodone release. Reduced C(max) and increased t max for ORF resulted in lower AQ scores for ORF compared with OC. ORF was associated with greater intranasal irritation than OC. These data suggest that ORF has a lower intranasal abuse potential than OC.
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 machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| 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 source (Gemma direct ou Codex distillé), 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 ».