کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8538987 | 1561124 | 2018 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Systemic exposure of vinpocetine in pregnant Sprague Dawley rats following repeated oral exposure: An investigation of fetal transfer
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The current study reports the systemic exposure and toxicokinetic (TK) parameters of vinpocetine and metabolite, apovincaminic acid (AVA), in pregnant Harlan Sprague Dawley rats, fetuses and amniotic fluid following oral gavage exposure of dams to 5 and 20 mg/kg vinpocetine from gestational day 6 to 18. Vinpocetine was absorbed rapidly in dams with a maximum plasma concentration (Cmax) reaching â¤Â 1.37 h. Predicted Cmax and area under the concentration versus time curve (AUC) increased less than proportionally to the dose. Vinpocetine was rapidly distributed to the peripheral compartment. More importantly, significant transfer of vinpocetine from dam to fetuses was observed with fetal Cmax and AUC â¥Â 55% of dams. Vinpocetine was cleared rapidly from dam plasma with an elimination half-life of â¤Â 4.02 h with no apparent dose-related effect. Vinpocetine was rapidly and highly metabolized to AVA with AVA plasma levels in dams â¥Â 2.7-fold higher than vinpocetine, although in the fetuses, AVA levels were much lower than vinpocetine. Comparison of current rat data with literature human data demonstrates that systemic exposure to vinpocetine in rats following repeated exposure to 5 mg/kg is similar to that following a single human relevant dose of 10 mg suggesting that the findings from the toxicology study may be relevant to humans.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 338, 1 January 2018, Pages 83-92
Journal: Toxicology and Applied Pharmacology - Volume 338, 1 January 2018, Pages 83-92
نویسندگان
Suramya Waidyanatha, Heather Toy, Natalie South, Seth Gibbs, Esra Mutlu, Brian Burback, Barry S. McIntyre, Natasha Catlin,