Platinum pharmacokinetics in mice following inhalation of cisplatin dry powders with different release and lung retention properties
| Autor: | Nathalie Wauthoz, Rémi Rosiere, Romain Merlos, Karim Amighi, Vincent Levet |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Cmax
Pharmaceutical Science 02 engineering and technology Pharmacology Kidney Polyethylene Glycols Mice 03 medical and health sciences 0302 clinical medicine Pharmacokinetics In vivo Administration Inhalation medicine Animals Particle Size Lung Platinum Cisplatin Inhalation Chemistry Inhaler Dry Powder Inhalers 021001 nanoscience & nanotechnology Controlled release Drug Liberation medicine.anatomical_structure Delayed-Action Preparations 030220 oncology & carcinogenesis Administration Intravenous Female Powders Rheology 0210 nano-technology medicine.drug |
| Zdroj: | International Journal of Pharmaceutics. 517:359-372 |
| ISSN: | 0378-5173 |
| DOI: | 10.1016/j.ijpharm.2016.12.037 |
| Popis: | Pharmacokinetics of cisplatin administered by the pulmonary route were established in mice using dry powders inhaler (DPI) formulations showing immediate (F1) and controlled release (CR, solid lipid microparticles) in vitro, without (F2) or with PEGylated excipients (F3, F4). Formulation administration was realized using dry powder blends (correspondingly named thereafter F1B to F4B) able to reproducibly deliver particles in vivo using a DP-4M Dry Powder Insufflator™. Their platinum pharmacokinetics were established over 48 h in lungs, total blood and non-target organs vs. IV and endotracheal nebulization (EN). EN and F1B were rapidly distributed from the lungs (t1/2i 2.6 and 5.0 min). F2B was eliminated in ∼1 h (t1/2i 9.0 min). F3B lung retention was sustained for ∼7 h (t1/2i 59.9 min), increasing lung AUC 11-, 4- and 3-fold vs. IV, F1B and F2B. Total blood tmax were higher and AUC and Cmax lower using the pulmonary route vs. IV. Kidney Cmax was reduced 6-, 2- and 3-fold for F1B, F2B and F3B. AUC in kidneys were 2- to 3-fold lower for F1B and F2B vs. IV but comparable for IV vs. F3B, probably because of kidney saturation. PEGylated solid lipid microparticles provided cisplatin particles with interesting lung retention and CR properties. |
| Databáze: | OpenAIRE |
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