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Pharmacokinetics and safety of paclitaxel delivery into porcine airway walls by a new endobronchial drug delivery catheter
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...
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Published in: | Respirology (Carlton, Vic.) Vic.), 2018-04, Vol.23 (4), p.399-405 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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 2.5 mg/mL in 10 healthy pigs), saline (14 injections in 2 healthy pigs) or Abraxane (ABX) (24 injections of 0.5 mg/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 28 days post‐injection.
Results
Injection of generic PTX directly into the bronchial wall at doses up to 1.5 mg/mL only caused minimal tissue injury. Dose‐limiting tissue reaction was observed at 2.5 mg/mL. Plasma PTX was detectable for up to 5 days but not at 28 days, with area under the curve (AUC)(0‐5d) 20‐ to 50‐fold lower than the AUC(0‐∞) of 6300 ng h/mL for the approved intravenous dose. At 7 and 28 days 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 |
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ISSN: | 1323-7799 1440-1843 |
DOI: | 10.1111/resp.13214 |