Abstract LB-165: Safety and pharmacokinetics of liposomal curcumin in healthy subjects:A randomized placebo-controlled double blind first-in human study.
Notice bibliographique
Résumé
Abstract Purpose: Curcumin exerts anti-proliferative and pro-apoptotic effects against various tumors in vitro and in vivo, and it has been found to suppress carcinogenesis in various organs. A liposomal curcumin formulation was developed enabling intravenous application. Methods: 50 healthy male or female subjects between 18 and 45 years were allocated to receive single ascending doses of liposomal curcumin as a continuous infusion over 120 min. Dose levels ranged from 10 to 400 mg/m2. Within each dose group one subject was randomized to receive placebo. A premedication of intravenous diphenhydramine and dexamethasone or diphenhydramine alone was administered to prevent hypersensitivity reactions. Pharmacokinetic assessments included plasma and urine levels of Curcumin and tetrahydrocurcumin (THC), the active metabolite of Curcumin and were analyzed by a validated LC/MS/MS method. Safety assessments included monitoring for adverse events, laboratory safety parameters with special focus on hemolysis, vital signs and ECG. Results and Conclusions: Liposomal curcumin infusions were tolerated without clinical symptoms. At the maximum tolerated dose of 400 mg/m2 of liposomal curcumin, transient increases in erythrocyte mean cell volume, echinocyte formation, and increased plasma lactate were observed. Markers of hemolysis (HBDH, potassium, haptoglobin, LDH, erythrocytes, Hb) did not change significantly, however, a tendency of erythrocyte loss (-0.5 T/l) was observed. At a dose of 120 mg/m2 intermittent echinocyte formation of some erythrocytes was evident. Curcumin and THC levels were established rapidly forming a plateau during infusion with Cmax for curcumin ranging between 42 ± 22 and 2359 ± 412 ng/mL for doses of 10 to 400mg/m2, respectively. Cmax for THC was 7.1 - 15.8-fold lower than Cmax of curcumin. Upon termination of infusion Curcumin and THC were rapidly cleared from plasma with a mean residence time of 0.62 hr for curcumin and 1.69 hr for THC. Urinary curcumin levels accounted for <0.12% of total systemic clearance.Conclusions: Relevant plasma levels of Curcumin were achieved by infusion of liposomal curcumin over 120 min. A continuous infusion (eg 24h) seems appropriate to achieve sustained exposure to curcumin. 120 mg liposomal curcumin/m2 is proposed as safe starting dose for phase I studies in patients with solid tumors. Citation Format: Angela Storka, Michael Wolzt, Brigitta Vcelar, Gordon Bolger, Muhammed Majeed, Lawrence Helson. Safety and pharmacokinetics of liposomal curcumin in healthy subjects:A randomized placebo-controlled double blind first-in human study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-165. doi:10.1158/1538-7445.AM2013-LB-165
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 | 0,002 | 0,000 |
| 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) | 0,000 | 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 ».