Docetaxel accumulates in lymphatic circulation following subcutaneous delivery compared to intravenous delivery in rats

Deanna R. Worley, Ryan J. Hansen, Luke Anthony Wittenburg, Laura S. Chubb, Daniel L. Gustafson

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5071-5078
Number of pages8
JournalAnticancer Research
Volume36
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

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Keywords

  • Carboplatin pharmacokinetics
  • Docetaxel pharmacokinetics
  • Lymph
  • Subcutaneous administration

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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