title: Docetaxel Accumulates in Lymphatic Circulation Following Subcutaneous Delivery Compared to Intravenous Delivery in Rats.
abstract: The circulatory pathway for particles deposited outside of blood capillaries has not been well characterized for non-traditionally-delivered chemotherapeutics.
  
  
  
  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.
  
  
  
  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 t1/2in blood. Carboplatin demonstrates a dose-dependent increase in plasma Cmaxregardless of delivery route; the total carboplatin exposure over 24 h in lymph and plasma are comparable.
  
  
  
  Subcutaneous docetaxel achieves lymphatic accumulation greater than that of i.v. delivery.
authors: Department of Clinical Sciences, Colorado State University, Fort Collins, CO, U.S.A. dworley@colostate.edu.|Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, U.S.A.
authors: Deanna R
authors: DR
authors: Worley
authors: Department of Clinical Sciences, Colorado State University, Fort Collins, CO, U.S.A.|Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, U.S.A.
authors: Ryan J
authors: RJ
authors: Hansen
authors: Department of Clinical Sciences, Colorado State University, Fort Collins, CO, U.S.A.|Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, U.S.A.
authors: Luke A
authors: LA
authors: Wittenburg
authors: Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, U.S.A.
authors: Laura S
authors: LS
authors: Chubb
authors: Department of Clinical Sciences, Colorado State University, Fort Collins, CO, U.S.A.|Flint Animal Cancer Center, Colorado State University, Fort Collins, CO, U.S.A.
authors: Daniel L
authors: DL
authors: Gustafson
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016190:Carboplatin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000077143:Docetaxel; D006207:Half-Life; D007279:Injections, Subcutaneous; D008196:Lymph / Q000378:metabolism*; D008297:Male; D017207:Rats, Sprague-Dawley; D043823:Taxoids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D016190:Carboplatin
keywords: Lymph; carboplatin pharmacokinetics; docetaxel pharmacokinetics; subcutaneous administration