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1.
Article in English | MEDLINE | ID: mdl-28346885

ABSTRACT

Ganoderic acid A (GAA), an active triterpenoid of the traditional Chinese herbal medicine Lingzhi, has been reported to exhibit antinociceptive, antioxidative, and anti-cancer activities. The present study aims to establish a sensitive and rapid UPLC-MS/MS method for studying the plasma and brain pharmacokinetics of GAA in rats. The analytes were separated on a C18 column eluted with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at 0.3mL/min. The eluate was monitored by a mass detector using an MRM (m/z, 515.3-285.1) model in negative electrospray ionization. The calibration curve showed good linearity (r2>0.99), with limits of detection and quantification of 0.25 and 2.00 nmol/L, respectively. The intra- and inter-day precision and accuracy were less than 9.99% and ranged from 97.45% to 114.62%, respectively. The extraction recovery from plasma was between 92.89% and 98.87%. GAA was found to be stable in treated samples at room temperature (22°C) for 12h and in plasma at -20°C for 7d. The developed method was successfully applied to a pharmacokinetic study of GAA in rats. GAA could be rapidly absorbed into the circulation (Tmax, 0.15h) and eliminated relatively slowly (t1/2, 2.46h) after orally dosing, and could also be detected in the brain lateral ventricle (Tmax, 0.25h and t1/2, 1.40h) after intravenously dosing. The absolute oral bioavailability and brain permeability of GAA were estimated to be 8.68% and 2.96%, respectively.


Subject(s)
Brain/metabolism , Chromatography, High Pressure Liquid/methods , Drugs, Chinese Herbal/pharmacokinetics , Heptanoic Acids/blood , Heptanoic Acids/cerebrospinal fluid , Lanosterol/analogs & derivatives , Tandem Mass Spectrometry/methods , Analgesics/blood , Analgesics/cerebrospinal fluid , Animals , Antineoplastic Agents, Phytogenic/blood , Antineoplastic Agents, Phytogenic/cerebrospinal fluid , Antioxidants/pharmacokinetics , Lanosterol/blood , Lanosterol/cerebrospinal fluid , Limit of Detection , Male , Microdialysis/methods , Rats, Sprague-Dawley
2.
Clin Neuropharmacol ; 14(3): 256-61, 1991 Jun.
Article in English | MEDLINE | ID: mdl-1906375

ABSTRACT

The capability of pravastatin and lovastatin, HMG-CoA reductase inhibitors likely to be taken chronically for hypercholesterolemia, to cross the blood-brain barrier was investigated in normal male volunteers. Lovastatin, which is lipophilic, was detected in cerebrospinal fluid (CSF) at concentrations that may have a pharmacologic effect. Pravastatin, which is hydrophilic, was not detected in CSF. It is concluded that pravastatin may have less potential for causing CNS-related side effects than lovastatin.


Subject(s)
Anticholesteremic Agents/cerebrospinal fluid , Heptanoic Acids/cerebrospinal fluid , Lovastatin/cerebrospinal fluid , Naphthalenes/cerebrospinal fluid , Adult , Anticholesteremic Agents/pharmacokinetics , Blood-Brain Barrier , Heptanoic Acids/pharmacokinetics , Humans , Lovastatin/pharmacokinetics , Male , Naphthalenes/pharmacokinetics , Pravastatin , Reference Values
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