التفاصيل البيبلوغرافية
| العنوان: |
Preclinical Pharmacokinetics, Tissue Distribution, and Plasma Protein Binding of Sodium (±)-5-Bromo-2-(α-Hydroxypentyl) Benzoate (BZP), an Innovative Potent Anti-ischemic Stroke Agent |
| المؤلفون: |
Gao-Ju Wang, Jingyao Wei, Xin Tian, Yu-Hai Zhang, Junbiao Chang, Bing-Jie Liu, Hong-Meng Li, Hai-Ling Qiao |
| المصدر: |
Frontiers in Pharmacology |
| بيانات النشر: |
Frontiers Media SA, 2016. |
| سنة النشر: |
2016 |
| مصطلحات موضوعية: |
Metabolite, Sodium, metabolite, tissue distribution, chemistry.chemical_element, Pharmacology, 030226 pharmacology & pharmacy, Beagle, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pharmacokinetics, In vivo, medicine, Distribution (pharmacology), Pharmacology (medical), Br-NBP, Original Research, Kidney, plasma protein binding, BZP, In vitro, medicine.anatomical_structure, chemistry, pharmacokinetics, 030217 neurology & neurosurgery |
| الوصف: |
Sodium (±)-5-bromo-2-(α-hydroxypentyl) benzoate (BZP) is a potential cardiovascular drug and exerts potent neuroprotective effect against transient and long-term ischemic stroke in rats. BZP could convert into 3-butyl-6-bromo-1(3H)-isobenzofuranone (Br-NBP) in vitro and in vivo. However, the pharmacokinetic profiles of BZP and Br-NBP still have not been evaluated. For the purpose of investigating the pharmacokinetic profiles, tissue distribution, and plasma protein binding of BZP and Br-NBP, a rapid, sensitive, and specific method based on liquid chromatography coupled to mass spectrometry (LC-MS/MS) has been developed for determination of BZP and Br-NBP in biological samples. The results indicated that BZP and Br-NBP showed a short elimination half-life, and pharmacokinetic profile in rats (3, 6, and 12 mg/kg; i.v.) and beagle dogs (1, 2, and 4 mg/kg; i.v.gtt) were obtained after single dosing of BZP. After multiple dosing of BZP, there was no significant accumulation of BZP and Br-NBP in the plasma of rats and beagle dogs. Following i.v. single dose (6 mg/kg) of BZP to rats, BZP and Br-NBP were distributed rapidly into all tissues examined, with the highest concentrations of BZP and Br-NBP in lung and kidney, respectively. The brain distribution of Br-NBP in middle cerebral artery occlusion (MCAO) rats was more than in normal rats (P < 0.05). The plasma protein binding degree of BZP at three concentrations (8000, 20,000, and 80,000 ng/mL) from rat, beagle dog, and human plasma were 98.1–98.7, 88.9–92.7, and 74.8–83.7% respectively. In conclusion, both BZP and Br-NBP showed short half-life, good dose-linear pharmacokinetic profile, wide tissue distribution, and different degree protein binding to various species plasma. This was the first preclinical pharmacokinetic investigation of BZP and Br-NBP in both rats and beagle dogs, which provided vital guidance for further preclinical research and the subsequent clinical trials. |
| اللغة: |
English |
| تدمد: |
1663-9812 |
| DOI: |
10.3389/fphar.2016.00255 |
| URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b1f098daf63bc2de5a8256c85041f45 |
| Rights: |
OPEN |
| رقم الانضمام: |
edsair.doi.dedup.....4b1f098daf63bc2de5a8256c85041f45 |
| قاعدة البيانات: |
OpenAIRE |