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标题：Pharmacokinetics of Exenatide in nonhuman primates following its administration in the form of sustained-release PT320 and Bydureon
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作者：Yazhou Li ; Kelli L. Vaughan ; David Tweedie 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-10
DOI：10.1038/s41598-019-53356-2
出版社：Springer Nature
摘要：The time-dependent (30 min - day 84) plasma profile of PT320, a sustained-release (SR)-Exenatide formulation under clinical development for treatment of neurodegenerative disorders, was evaluated in nonhuman primates after a single subcutaneous dose and was compared to Bydureon. Exenatide release from PT320 exhibited a triphasic pharmacokinetic profile. An initial peak occurred at 3 hr post-administration, a secondary peak at 5 days, and achievement of Exenatide steady-state plasma levels from day 10-28. Systemic exposure increased across PT320 doses, and Exenatide levels were maintained above the therapeutic threshold prior to achieving a steady-state. In contrast, Exenatide release from Bydureon exhibited a biphasic profile, with an initial plasma peak at 3 hr, followed by a rapid decline to a sub-therapeutic concentration, and a gradual elevation to provide a steady-state from day 35-49. Exenatide total exposure, evaluated from the area under the time-dependent Exenatide concentration curve, was similar for equivalent doses of PT320 and Bydureon. The former, however, reached and maintained steady-state plasma Exenatide levels more rapidly, without dipping to a sub-therapeutic concentration. Both SR-Exenatide formulations proved well-tolerated and, following a well-regulated initial release burst, generated steady-state plasma levels of Exenatide, but with PT320 producing continuous therapeutic Exenatide levels and more rapidly reaching a steady-state.