Platinum pharmacokinetics in mice following inhalation of cisplatin dry powders with different release and lung retention properties.

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 F1 B to F4 B ) 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 F1 B were rapidly distributed from the lungs ( t 1/2 i 2.6 and 5.0 min). F2 B was eliminated in ∼1 h ( t 1/2 i 9.0 min). F3 B lung retention was sustained for ∼7 h ( t 1/2 i 59.9 min), increasing lung AUC 11-, 4- and 3-fold vs. IV, F1 B and F2 B . Total blood t max were higher and AUC and C max lower using the pulmonary route vs. IV. Kidney C max was reduced 6-, 2- and 3-fold for F1 B , F2 B and F3 B . AUC in kidneys were 2- to 3-fold lower for F1 B and F2 B vs. IV but comparable for IV vs. F3 B , probably because of kidney saturation. PEGylated solid lipid microparticles provided cisplatin particles with interesting lung retention and CR properties. [ABSTRACT FROM AUTHOR]