UC Davis

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 (t_1/2) 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.