Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration.
The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified.
a Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology , Beijing Hospital , Beijing 100730 , China.
Wei
W
Xue
b Department of Pharmacy , Peking University People's Hospital , Beijing 100044 , China.
Yang
Y
Liu
a Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology , Beijing Hospital , Beijing 100730 , China.
Wen-Yuan
WY
Qi
a Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology , Beijing Hospital , Beijing 100730 , China.
Yan
Y
Gao
a Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology , Beijing Hospital , Beijing 100730 , China.
Min
M
Li
a Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology , Beijing Hospital , Beijing 100730 , China.
Ai-Xin
AX
Shi
a Beijing Key Laboratory of Drug Clinical Risk and Personalized Medication Evaluation, Department of Clinical Pharmacology , Beijing Hospital , Beijing 100730 , China.
Ke-Xin
KX
Li
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D036145:Ginsenosides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000378:metabolism; D020547:Lateral Ventricles / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D015394:Molecular Structure; D005894:Panax / Q000737:chemistry*; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods
D036145:Ginsenosides; C035054:ginsenoside Rg1
Ginsenoside Rg1; blood-brain barrier; blood-cerebrospinal fluid barrier; in vivo recovery; intracerebral pharmacokinetics