title: State of insulin self-association does not affect its absorption from the pulmonary route.
abstract: This study is designed to compare and contrast the pulmonary absorption profiles of monomeric and hexameric insulin in the presence or absence of ethylene diamine tetraacetic acid (EDTA) or n-tetradecyl-beta-d-maltoside (TDM). The pulmonary absorption of two forms of insulin was studied by monitoring the changes in plasma insulin and glucose levels after intratracheal administration of monomeric or hexameric insulin into anesthetized rodents. EDTA or TDM was added to the formulation in order to evaluate if either of these agents has effects on the rate and extent of pulmonary absorption of monomeric and hexameric insulin. The biochemical changes that may occur after acute administration of TDM-based formulation have also been investigated by estimating lung injury markers in bronchoalveolar lavage fluid. A dose-dependent increase in the plasma insulin and decrease in plasma glucose levels was observed when increasing concentrations of hexameric or monomeric insulin were administered via the pulmonary route. Pulmonary administration of monomeric and hexameric insulin produced comparable absorption profiles in the presence or absence of EDTA or TDM. The bronchoalveolar lavage fluid analysis did not show differences in the levels of injury markers produced in TDM-treated rats and that produced in saline-treated rats, indicating no evidence for adverse effects of TDM in these short-term studies. Overall, in terms of rapidity of action and efficacy to reduce blood sugar, monomeric insulin did not provide advantages over hexameric insulin when administered via the pulmonary route.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, 1300 Coulter, Amarillo, TX 79106, USA.
authors.forename: Alamdar
authors.initials: A
authors.lastname: Hussain
authors.forename: Fakhrul
authors.initials: F
authors.lastname: Ahsan
mesh_terms: D000042:Absorption; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000737:chemistry; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000494:pharmacology; D061268:Insulin Lispro; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008320:Maltose / Q000031:analogs & derivatives* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000277:Adjuvants, Pharmaceutic; D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro; C459187:tetradecyl maltoside; D008320:Maltose; D004492:Edetic Acid