Docetaxel Accumulates in Lymphatic Circulation Following Subcutaneous Delivery Compared to Intravenous Delivery in Rats
| Autor: | Daniel L. Gustafson, Luke Anthony Wittenburg, Ryan J. Hansen, Laura S. Chubb, Deanna R. Worley |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Cancer Research Docetaxel 02 engineering and technology Pharmacology Carboplatin Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine Jugular vein Medicine subcutaneous administration Subcutaneous General Medicine 021001 nanoscience & nanotechnology Lymphatic system Oncology Area Under Curve 030220 oncology & carcinogenesis Administration Circulatory system Administration Intravenous Taxoids Lymph Intravenous 0210 nano-technology therapeutics Half-Life medicine.drug Injections Subcutaneous Oncology and Carcinogenesis Cmax Antineoplastic Agents Article docetaxel pharmacokinetics Injections 03 medical and health sciences Pharmacokinetics Animals Oncology & Carcinogenesis neoplasms business.industry carboplatin pharmacokinetics Rats chemistry Sprague-Dawley business |
| Zdroj: | Anticancer research, vol 36, iss 10 |
| ISSN: | 1791-7530 0250-7005 |
| DOI: | 10.21873/anticanres.11076 |
| Popis: | Background: The circulatory pathway for particles deposited outside of blood capillaries has not been well characterized for non-traditionally-delivered chemotherapeutics. Materials and Methods: Blood and lymph pharmacokinetics of docetaxel (5 mg/kg) and carboplatin (14 and 28 mg/kg) following subcutaneous (s.c.) versus intravenous (i.v.) delivery were determined in a rodent model with catheterizations of both the thoracic lymphatic duct and jugular vein for prolonged synchronous blood and lymph sampling. Results: Subcutaneous docetaxel demonstrates preferential lymphatic accumulation based on the area under the time-concentration curve (AUC0-24h) whereas i.v. docetaxel resulted in a greater plasma maximum concentration measured (Cmax). The apparent elimination half-life (t1/2) in lymph for docetaxel is greater following i.v. or s.c. delivery compared to t1/2 in blood. Carboplatin demonstrates a dose-dependent increase in plasma Cmax regardless of delivery route; the total carboplatin exposure over 24 h in lymph and plasma are comparable. Conclusion: Subcutaneous docetaxel achieves lymphatic accumulation greater than that of i.v. delivery. |
| Databáze: | OpenAIRE |
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