Great variation in bioavailability and elimination of Meropenem is increased in critically ill children especially when they receive Continuous Renal Replacement Therapy (CRRT). Introduction: Meropenem is one of the most widely used classes in pediatric intensive care for his broad-spectrum activity in multidrug-resistant bacterial infections. Oualha 4ġ EA 7323-Pharmacologie et Évaluation des Thérapeutiques chez l’Enfant et La Femme Enceinte, Université de Paris, France 2 Laboratoire de Microbiologie, CHU Necker-Enfants Malades, Assistance Publique des Hôpitaux de Paris, France 3 Pediatric and Neonatal Intensive Care Unit, Armand Trousseau Hospital, APHP Sorbonne University -, Paris, France 4 Pediatric Intensive Care Unit, CHU Necker-Enfants Malades -, Paris, France Meropenem population pharmacokinetics and dosing regimen optimization in critically ill children receiving continuous renal replacement therapy Keywords: rapamycin, osteoarthritis, intra-articular administration.
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free rapamycin with lower systemic diffusion. In vivo, IA administration of 10 μM rapamycin NPs increased its local residency vs. Rapamycin NPs did not induce cytotoxicity on articular cells at 10 μM. Histology revealed no knee injury.ĭiscussion/Conclusion: In vitro, rapamycin (10 μM) did not induce articular cytotoxicity and reduced IL1β's phlogistic effects.
T1/2 and MRT were higher after NPs than free rapamycin injections: 57.8–5.0 h, vs. We observed a difference between AUCIA free and AUCIA NP (373 μg/min/L) concerning synovium. In vivo, we determined (10 μM) an AUC higher for IV free rapamycin than for IA injection (AUCIA free and AUCIA NP), with respectively 4248, 28, and 74 μg/min/L in blood. Rapamycin NPs showed similar dose-dependent toxicity on articular cells. No difference was observed for autophagic genes in the three cellular types, but the IL1β-induced MMP13 level decreased. Results: In vitro, we observed the concentration-dependent toxicity of free rapamycin for chondrocytes, synoviocytes, and MSCs. We finally studied in vivo pharmacokinetic parameters of free (IV & IA) or NPs-loaded rapamycin (IA) (10 μM) injections in blood and synovial tissue in rat knees: AUC, T1/2, and MRT.
We also developed rapamycin-loaded nanoparticles (NPs) for IA injection to assess NPs' cytotoxicity vs free rapamycin. We then evaluated autophagic (beclin1 and Atg7) and catabolic (MMP13) genes with 10 μM rapamycin exposure for 24 h. Material and methods: We performed in vitro cytotoxicity on human chondrocytes, synoviocytes, and mesenchymal stem cells (MSCs) after 24 h exposure in hypoxia and normoxia with various rapamycin concentrations (10 nM to 100 μM). It is a candidate (10 μM) for experimental intra-articular (IA) treatment of osteoarthritis (OA), autophagy being defective in OA. Introduction: Rapamycin, an immunosuppressant, is a mTOR inhibitor leading to autophagy restoration. Gambier 1ġ CNRS, Imopa & Laboratoire de Pharmacologie, Toxicologie et Pharmacovigilance, CHRU - Nancy, Université de Lorraine, France 2 Cithefor - Nancy, Université de Lorraine, France Designing dedicated rapamycin nanoparticles for articular vectorization: A holistic pharmacological approachĮ.
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