Docetaxel Accumulates in Lymphatic Circulation Following Subcutaneous Delivery Compared to Intravenous Delivery in Rats

作者：Worley Deanna R^*; Hansen Ryan J; Wittenburg Luke A; Chubb Laura S; Gustafson Daniel L

来源：Anticancer Research, 2016, 36(10): 5071-5078.

DOI：10.21873/anticanres.11076

• Lymph
• subcutaneous administration
• docetaxel pharmacokinetics
• carboplatin pharmacokinetics

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 (AUC(0-24h)) whereas i.v. docetaxel resulted in a greater plasma maximum concentration measured (C-max). The apparent elimination half-life (t1/2) in lymph for docetaxel is greater following i.v. or s.c. delivery compared to t(1/2) in blood. Carboplatin demonstrates a dose-dependent increase in plasma C-max 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.

• 出版日期2016-10