Pharmacokinetics and safety of paclitaxel delivery into porcine airway walls by a new endobronchial drug delivery catheter

Hisashi Tsukada, Plamena Entcheva-Dimitrov, Armin Ernst, Samaan Rafeq, John H. Keating, Kirk P. Seward, Lonny Yarmus

Research output: Contribution to journalArticle

Abstract

Background and objective: Intratumoral administration of chemotherapeutic agents is a treatment modality that has proven efficacious in reducing the recurrence of tumours and increases specificity of treatment while minimizing systemic side effects. Direct intratumoral injection of malignant airway obstruction has potential therapeutic benefits but tissue drug concentrations and side-effect profiles are poorly understood. Methods: Bronchial wall injection of generic paclitaxel (PTX) (102 injections of 0.05, 0.5, 1.5 or 2.5mg/mL in 10 healthy pigs), saline (14 injections in 2 healthy pigs) or Abraxane (ABX) (24 injections of 0.5mg/mL in 4 healthy pigs) was performed with a microneedle infusion catheter. Local histopathology, plasma and tissue PTX concentrations were evaluated at 7, 20 or 28days post-injection. Results: Injection of generic PTX directly into the bronchial wall at doses up to 1.5mg/mL only caused minimal tissue injury. Dose-limiting tissue reaction was observed at 2.5mg/mL. Plasma PTX was detectable for up to 5days but not at 28days, with area under the curve (AUC)(0-5d) 20- to 50-fold lower than the AUC(0-∞) of 6300ngh/mL for the approved intravenous dose. At 7 and 28days post-injection, bronchial PTX tissue concentrations were above a 10-nmol/L cancer therapeutic level. PTX was not found in peripheral tissues. Similar results were observed between ABX and generic PTX. Conclusion: Results of these studies confirm the administration of PTX directly into the bronchial wall is safe and feasible. PTX was detectable in plasma for <7days but tissue concentrations remained therapeutic throughout the follow-up period.

Original languageEnglish (US)
JournalRespirology
DOIs
StateAccepted/In press - Jan 1 2017

Keywords

  • Airway obstruction
  • Bronchoscopy and interventional techniques
  • Interventional pulmonary
  • Lung cancer

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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