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Intranasal Delivery of Recombinant Human Parathyroid Hormone [hPTH (1-34)], Teriparatide in Rats 

Authors: Remigius U. Agu a;  Satyanarayana Valiveti a;  D. Caroline Earles a;  Mitchell Klausner b;  Patrick J. Hayden b;  Daniel P. Wermeling ac; Audra L. Stinchcomb a
Affiliations:   a College of Pharmacy, University of Kentucky, Lexington, Kentucky, USA
b MatTek Corporation, Ashland, Massachusetts, USA
c Intranasal Technology, Inc., Lexington, Kentucky, USA
DOI: 10.1081/ERC-200035957
Publication Frequency: 4 issues per year
Published in: journal Endocrine Research, Volume 30, Issue 3 January 2004 , pages 455 - 467
Subject: Endocrinology;
Formats available: HTML (English) : PDF (English)
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Abstract

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®. 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® tissue model. The intranasal absorption of hPTH (1-34) was rapid; the absorption rate constants (agr) 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 (Cmax): 151 ± 24 pg/mL (without BSA) and 176 ± 37 (with 1% BSA) were attained within approximately 15 min. The intranasal bioavailabilities (Fabs) 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® 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).
Keywords: Human parathyroid hormone; Teriparatide; Nasal absorption; Pharmacokinetics; Nasal tissue; Nasal toxicity
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