The pulmonary pharmacokinetics and anti-inflammatory effects after intratracheal and intravenous administration of Chuankezhi injection

Abstract

Background: Chuankezhi injection (CKZ) is a traditional Chinese medicine for the treatment of respiratory diseases and has been often used off-label as a nebulization therapy. However, little is known about the aerosolization performance and pulmonary fate of the inhaled CKZ. This study aimed to evaluate the aerodynamic characteristics of nebulizer generated aerosols and to compare the properties of pharmacokinetics, lung distribution and anti-inflammation effects of CKZ after intratracheal and intravenous administration. Methods: The nebulization performance was evaluated in vitro based on the aerodynamic particle size distribution and aerosol output. The concentrations of epimedins A, B, C and icariin, the main active ingredients of CKZ, in plasma, bronchoalveolar lavage fluids (BALF) and lung tissues were measured by LC-MS/MS analysis. The pulmonary anti-inflammatory efficacy were tested using LPS-induced pulmonary inflammation mice model as indicated by the total cells counts, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in BALF. Results: The aerosols of CKZ generated by a commercial nebulizer showed excellent aerodynamic properties and delivery output. Following intratracheal instillation of CKZ, epidemins A, B and C, and icariin, were absorbed into the bloodstream with the mean absorption time varying from 101.8 min to 271.8 min, and their absolute bioavailabilities ranging from 26.4 % to 104 %. The instillation of CKZ increased the lung to plasma concentration ratios by 25.5–718 folds compared to intravenous administration, leading to improved and prolonged local anti-inflammatory effects. Conclusion: Nebulization therapy of CKZ could be a promising alternative to the injectable counterpart.

Keywords

• Chuankezhi
• Nebulization therapy
• Pulmonary pharmacokinetics
• Bioavailability
• Pulmonary inflammation