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
Subject:
Endocrinology;
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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 (
) 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).
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| Keywords: Human parathyroid hormone; Teriparatide; Nasal absorption; Pharmacokinetics; Nasal tissue; Nasal toxicity |
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) 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).
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