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• W2003128875 startingPage "957" @default.
• W2003128875 abstract "This study was performed to examine the absorption potential of polyethylene glycol (PEG)-modified salmon calcitonin (sCT) in rats administered via the nasal route. Previous studies have used relatively high molecular weight polyethylene glycols (e.g., ≥5000 daltons) for PEG-modification of sCT to provide increased metabolic stability and biological half-life. Unlike these studies, the present study utilized a low molecular weight succinimidyl-propionated monomethoxy-poly(ethylene glycol) (MW 2000). It was hypothesized that the potential for membrane transport would not be significantly altered due to a relatively small increase in the molecular size while the metabolic stability would be enhanced due to resistance to proteolytic degradation. After PEG-modification of sCT, the mono-PEG positional isomer (mono-PEG2k-sCT) was separated from di-PEG2k-sCT, tri-PEG2k-sCT, and unmodified sCT by size exclusion chromatography. The mono-PEG2k-sCT and unmodified sCT were radioiodinated, and the resulting 125I-sCT and 125I-mono-PEG2k-sCT were separated from free iodine by RP HPLC and confirmed by MALDI-TOF MS. The 125I-sCT and 125I-mono-PEG2k-sCT were administered to rats via the nasal route, and serial blood, tissue, and urine samples were taken for up to 36 h for the determination of radioactivity. Mono-PEG2k-sCT exhibited significantly increased AUC (20638 vs. 3650 ng·min/ml), tmax (520 vs. 77 min), and t1/2,λz (923 vs. 199 min) compared with unmodified sCT. This study demonstrates that mono-PEG2k-sCT is absorbed systemically when given by the intranasal route, exhibiting altered absorption kinetics compared with unmodified sCT." @default.
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• W2003128875 date "2004-01-01" @default.
• W2003128875 modified "2023-10-03" @default.
• W2003128875 title "Nasal Absorption and Pharmacokinetic Disposition of Salmon Calcitonin Modified with Low Molecular Weight Polyethylene Glycol" @default.
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• W2003128875 doi "https://doi.org/10.1248/cpb.52.957" @default.
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