Toxicokinetic Study of Recombinant Human Heparin-Binding Epidermal Growth Factor-Like Growth Factor (rhHB-EGF) in Female Sprague Dawley Rats
Purpose To determine the toxicity and pharmacokinetics of recombinant heparin-binding epidermal growth factor-like growth factor in female Sprague Dawley rats following intra-bladder and intravenous administration. Materials and Methods rhHB-EGF was administered once daily for 6 or 27 days at doses...
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Published in | Pharmaceutical research Vol. 25; no. 3; pp. 542 - 550 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Boston
Springer US
01.03.2008
Springer Springer Nature B.V |
Subjects | |
Online Access | Get full text |
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Summary: | Purpose
To determine the toxicity and pharmacokinetics of recombinant heparin-binding epidermal growth factor-like growth factor in female Sprague Dawley rats following intra-bladder and intravenous administration.
Materials and Methods
rhHB-EGF was administered once daily for 6 or 27 days at doses of 3, 10, or 30 μg/kg.
125
I-rhHB-EGF was administered on day 7 or 28 for pharmacokinetic analysis. Toxicity was assessed by general appearance and behavior, gross necropsy, blood chemistry and microscopic evaluation.
Results
Plasma AUCss of [
125
I] rhHB-EGF equivalents following IB administration for 7 days were 4.28 ± 2.29, 7.75 ± 2.70, and 7.11 ± 1.42 ng ml
−1
h
−1
at doses of 3, 10, and 30 μg/kg, respectively. Following IV administration, the AUCss on day 7 increased from 27.0 ± 2.66 to 124 ± 5.09 and 385.11 ± 7.57 ng ml
−1
h
−1
with increasing the dose from 3 to 10 and 30 μg/kg. Similar AUCss data was obtained after 28 day administration. No toxicity was evident upon gross examination. Histologic examination revealed subacute inflammation and lymphocytic infiltration of the urinary bladder in animals from all groups dosed by the IB route.
Conclusions
Plasma and bladder concentrations of recombinant human [
125
I] rhHB-EGF equivalents were significantly lower following the IB route than following IV administration. Histologic tissue examination indicated no toxicity attributable to rhHB-EGF. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0724-8741 1573-904X |
DOI: | 10.1007/s11095-007-9392-3 |