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  • Title: Preparation, Pharmacokinetic Profile, and Tissue Distribution Studies of a Liposome-Based Formulation of SN-38 Using an UPLC-MS/MS Method.
    Author: Li K, Wang S.
    Journal: AAPS PharmSciTech; 2016 Dec; 17(6):1450-1456. PubMed ID: 26831446.
    Abstract:
    The application of 7-ethyl-10-hydroxycamptothecin (SN-38) in cancer treatment is limited by its low solubility. This study is to develop a liposome-entrapped formulation of SN-38 (LE-SN38) to solve the obstacle and to evaluate its pharmacokinetic profile in dogs and tissue distribution in mice. LE-SN38 which is more likely to be suitable for large-scale production was prepared by the carrier-deposition method. An UPLC-MS/MS method was used to determinate the concentration of SN-38 in this study. LE-SN38 was cleared rapidly from dog plasma within 1 h, and the AUC0-∞ values of three dosages of LE-SN38 indicated an apparent dose-dependent manner. As for the distribution study, the peak of SN-38 levels in most tissues were detected within 10 min after LE-SN38 administration. In addition, concentration of SN-38 in most tissues except kidney and heart in LE-SN38 group was higher than that in irinotecan hydrochloride (CPT-11) group generally, whereas the administrated CPT-11 had 20 times dosage compared to LE-SN38. LE-SN38 was rapidly eliminated from dog plasma and manifested linear dynamics in dose range of 0.411-1.644 mg/kg. The distribution behavior of SN-38 is altered in a liposome-based delivery system. At the same time, LE-SN38 has lower toxicity compared to CPT-11 in some degree.
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