Journal
ENDOCRINE RESEARCH
Volume 30, Issue 3, Pages 455-467Publisher
TAYLOR & FRANCIS INC
DOI: 10.1081/ERC-200035957
Keywords
human parathyroid hormone; teriparatide; nasal absorption; pharmacokinetics; nasal tissue; nasal toxicity
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The aim of this study was to explore the nasal route as an alternative to daily subcutaneous injections of hPTH (1-34). Anesthetized rats were surgically prepared and nasally dosed with aqueous solutions of hPTH (1-34). Plasma samples were assayed by radioimmunoassay and data generated fit to two- (intravenous) and one(intranasal) compartment pharmacokinetic models using WinNonlin(R). The toxicity of hPTH (1-34) solution administered to the rats was assessed by screening its effect on transepithelial electrical resistance, potential difference, paracellular marker permeation, tissue viability, and protein leakage using the EpiAirway(R) tissue model. The intranasal absorption of hPTH (1-34) was rapid; the absorption rate constants (alpha) were 33.2 +/- 24 h(-1) [without bovine serum albumin (BSA)] and 9.8 +/- 5.1 h(-1) (with 1% BSA). The maximum plasma concentrations (C-max): 151 +/- 24 pg/mL (without BSA) and 176 +/- 37 (with 1% BSA) were attained within approximately 15 min. The intranasal bioavailabilities (F-abs) were 12.1 +/- 3.4% (without BSA) and 17.6 +/- 1.5% (with 1% BSA). The hPTH (1-34) formulation administered to the rats had no detrimental effect on the EpiAirway(R) tissue epithelial electrical parameters and functional integrity. Based on the results of this study, the nasal route appears to be a prospective alternative to subcutaneous injections of hPTH (1-34).
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