Impact of formulation and methods of pulmonary delivery on absorption of parathyroid hormone (1-34) from rat lungs.
The aim of this work was to optimize the absorption of parathyroid hormone 1-34 (PTH) from the lungs by determining factors favoring its transport from the air spaces into the bloodstream. We simultaneously conducted pharmacokinetic and regional lung deposition studies in vivo in the rat following intratracheal administration of PTH in solution or dry powder form. Dry powders of PTH or albumin were prepared by spray-drying using lactose and dipalmitoylphosphatidylcholine (DPPC). Deposition in the trachea, peripheral, and central lobe sections was assessed after tissue grinding using albumin as a marker. The method of intratracheal instillation had a significant impact on PTH absorption from the lungs, and the deeper the deposition within the respiratory tract, the higher the absorption. Inhalation of the PTH powder resulted in high systemic bioavailability despite deposition of the formulation principally in upper airways. We demonstrated that the increased absorption resulted from DPPC that had permeation enhancer properties even though it was abundantly present locally in pulmonary surfactant. Optimization of PTH absorption from the lungs could be attained by targeting the peripheral lungs as well as codelivering DPPC.
Codrons
Valérie
V
Université catholique de Louvain, School of Pharmacy, Department of Pharmaceutical Technology, Avenue E. Mounier, 73 UCL 73.20, 1200 Brussels, Belgium.
Vanderbist
Francis
F
Ucakar
Bernard
B
Préat
Véronique
V
Vanbever
Rita
R
D000042:Absorption / Q000187:drug effects / Q000502:physiology; D000280:Administration, Inhalation; D000818:Animals; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar
D010281:Parathyroid Hormone; D010446:Peptide Fragments