RESUMEN

Aerosol inhalation delivery of cefazolin, a broad-spectrum first-generation cephalosporin antibiotic, was investigated. Inhalation system based on ultrasonic nebulizer was developed for the generation of dry cefazolin aerosol within mean particle diameter range 0.5-3.0 µm and mass concentration 0.01-3 µg/cm3. Pharmacokinetic measurements were carried out for the aerosolized form of cefazolin delivered in mice using nose-only chamber. Cefazolin concentrations in blood serum and in the lungs of mice were measured as a function of time by means of high performance liquid chromatography. Body-delivered dose depending on particle size, concentration and inhalation time as well as other pharmacokinetic parameters were determined. The antibacterial effect of aerosolized cefazolin was assessed through the aerosol inhalation treatment of mice infected with Klebsiella pneumoniae. Survival rate for infected mice after the treatment with cefazolin aerosol demonstrated high antibacterial efficiency of the inhalation delivery of cefazolin in comparison with intraperitoneal delivery.

Asunto(s)

Cefazolina , Nebulizadores y Vaporizadores , Administración por Inhalación , Aerosoles , Animales , Antibacterianos , Ratones , Tamaño de la Partícula

RESUMEN

Excipient-free isoniazid aerosol formation and pulmonary delivery in mice are studied. An evaporation-nucleation route is used for the generation of isoniazid aerosol. Particle diameters and number concentrations are measured with an aerosol spectrometer consisting of a diffusion battery, condensation chamber, and photoelectric counter. The pulmonary delivery of isoniazid particles is studied in both nose-only (NO) and whole-body (WB) inhalation chambers for the particle mean diameter and number concentration to be 600 nm and 6 × 106 cm-3, respectively. It is found that the rate of drug systemic absorption in the WB chamber is 27% higher than that for the NO one because of an additional consumption of drug orally from the fur in the WB chamber. The particle deposition efficiency ε in the mouse respiratory tract is measured as a function of mean diameter. The quantity ε is equal to 0.7 for the particle diameter d = 10 nm and decreases to 0.2 with the diameter increasing to 300 nm, and then, at d > 300 nm the deposition efficiency increases with diameter to 0.5 at d = 2000 nm. The bioavailability of the aerosol form of isoniazid (72 ±â€¯10%) is very close to that for the per-oral form (61 ±â€¯10%).

Asunto(s)

Antituberculosos , Isoniazida , Administración por Inhalación , Aerosoles , Animales , Antituberculosos/administración & dosificación , Antituberculosos/química , Antituberculosos/farmacocinética , Disponibilidad Biológica , Isoniazida/administración & dosificación , Isoniazida/química , Isoniazida/farmacocinética , Hígado/metabolismo , Pulmón/metabolismo , Masculino , Ratones , Tamaño de la Partícula , Distribución Tisular