药代动力学与实验治疗学杂志

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Development of Aqueous Based Formulation of Docetaxel: Safety and Pharmacokinetics in Patients with Advanced Solid Tumors

Ateeq Ahmad, Saifuddin Sheikh, Shoukath M Ali, Moghis U Ahmad, Mahesh Paithankar, Dipak Saptarishi, Kirti Maheshwari, Kirushna Kumar, Jeba Singh, GN Patel, Jayanti Patel, Ashish Mukhopadhay, Ritwik Pandey, Chinmoy Bose, Singh JK, Manisha Singh, Rahul Chowdhary, Prashant Kale and Imran Ahmad

A well characterized Nanosomal Docetaxel Lipid Suspension (NDLS) formulation was developed without using any detergent or toxic organic solvents to avoid hypersensitivity reactions caused by the marketed Taxotere® product. The lyophilized NDLS formulation was easily resuspended in water and found to be physically and chemically stable for 48 hours. Physico-chemical characterization of NDLS confirmed a homogeneous formulation with an average particle size of less than 100 nm. Percent Docetaxel association with lipids in NDLS formulation was found to be greater than 95%. The in-vitro release assay showed a sustained release of 25% Docetaxel after 4 hours and 100% Docetaxel release after 42 hours of incubation. Sub-chronic toxicity in mice and rats showed comparable safety to Taxotere®. However, a pharmacokinetics study in rats revealed greater systemic availability of Docetaxel after administration of NDLS compared to Taxotere®. Further, a comparative safety and pharmacokinetic crossover study at 75 mg/m2 of NDLS and Taxotere® in patients with advanced solid tumor also showed higher exposure of Docetaxel with NDLS formulation than patients treated with Taxotere® formulation