Vinorelbine liposomes injection results in greater tumor drug exposure compared to conventional vinorelbine in tumor-bearing nude mice
Notice bibliographique
Résumé
C109 Background: Conventional vinorelbine tartrate (VRL) is a lipophilic, cell-cycle-specific anticancer agent that inhibits tumor cell growth by disrupting microtubule assembly during metaphase. AlocrestTM (vinorelbine liposomes injection) is a proprietary sphingomyelin/cholesterol liposome (OPTISOMETM) encapsulated formulation of VRL with an extended circulating half-life and the potential for enhanced tumor tissue targeting, exposure, and antitumor activity. This study evaluated and compared the pharmacokinetic (PK) profiles and tissue distributions (TD) of Alocrest and VRL in tumor-bearing CD-1 female nude mice. Methods: Mice were subcutaneously implanted with MX-1 human breast tumors. When tumor volumes reached 150 mm3,twenty-four mice per group received a single IV bolus dose of 20 mg/kg (60 mg/m2) of either VRL (3H-VRL) or Alocrest (3H-Alocrest) via the tail vein in a vehicle volume of 10 µL/g body weight. Blood/plasma and tissue samples (gall bladder/bile, heart, kidneys, liver, lungs, muscle, ovaries, small intestine, spleen, and tumor) were collected at 5 min, 1 h, 4 h, 8 h, 24 h, and 96 h post dosing. The total radioactivity from parent compound and metabolites in tissue, VRLeq, was analyzed by liquid scintillation counting. Results: The concentrations of VRLeq in blood/plasma were higher after administration of Alocrest resulting in higher AUCinf in Alocrest-treated mice compared to VRL-treated mice. The steady state volume of distribution and clearance were lower for Alocrest compared to VRL, supporting slower distribution and removal of Alocrest from the plasma compartment. The TD profile of Alocrest showed that, depending on the tissue, VRLeq concentrations peaked at 4 or 8 hours compared to VRL Tmax at 5 minutes or 1 hour. Tumor AUClast values (h*mcg/g) for VRLeq were 1166 in the Alocrest group and 123 in the VRL group. The AUClast for Alocrest was 9.5-fold greater in the tumor, 7.0-fold higher in spleen, 2.4-fold higher in ovaries and 1.0-1.6-fold higher in most other tissues (lower in lung) compared to the AUClast for conventional VRL. The greatest amount of radioactivity as a percent of injected dose (%ID) following Alocrest was found in liver > spleen > tumor while following VRL the greatest %ID was in liver > kidneys > lungs > small intestine. The %ID following Alocrest peaked at 4 to 8 hours before declining except in tumor where %ID peaked at 24 hours and remained constant for up to 96 hours. Conclusions: Optisomal encapsulation of VRL, Alocrest, protects the drug from initial rapid distribution observed with conventional VRL and provides longer drug retention in the circulation. Alocrest results in targeted delivery of drug, accumulation of drug in tumor tissue, and gradual drug release over several days. These unique characteristics result in greater tumor drug exposure and the potential for enhanced anti-tumor activity without increased toxicity. Human clinical trials are ongoing at this time.
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 | 0,001 |
| 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 ».