Deanna R Worley1,2, Ryan J Hansen3,2, Luke A Wittenburg3,2, Laura S Chubb2, Daniel L Gustafson3,2. 1. Department of Clinical Sciences, Colorado State University, Fort Collins, CO, U.S.A. dworley@colostate.edu. 2. Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, U.S.A. 3. Department of Clinical Sciences, Colorado State University, Fort Collins, CO, U.S.A.
Abstract
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. Copyright
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. Copyright
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