[In vivo distribution and pharmacokinetics of multiple effective components contained in Panax notoginseng saponins after intratympanic administration].
OBJECTIVE
To investigate in vivo distribution and pharmacokinetics of ginsenoside Rb1 (Rb1), ginsenoside Rg1 (Rg1 ) and sanchinoside R1 (R1) after intratympanic administration (IT) or intravenous administration (IV) of Panax notoginseng saponions (PNS) solution, and provide a novel route for delivering traditional Chinese medicine (TCM) to the brain.


METHODS
The guinea pigs were employed as experimental animal. Perilymph (PL), cerebrospinal fluid (CSF), brain tissue and plasma were collected periodically after IT and IV of PNS solution. The concentrations of Rb1, Rg1 and R1 were measured by high performance liquid chromatography (HPLC), and statistic program DAS was applied to the calculation of pharmacokinetic parameters. The self-defined weighting coefficients based on area under curve (AUC) of each component were created to obtain the holistic pharmacokinetic profiles of PNS. The integrated pharmacokinetic parameters were then calculated from non-compartmental model analysis.


RESULTS
Rb1, Rg1 and R1 diffused through the round window membrane into PL of the inner ear, and then transported to the brain after IT of PNS solution. However, the pharmacokinetic parameters showed significant differences between the three components. Based on the self-defined AUC weighting coefficients integration approach, the holistic pharmacokinetic profiles of PNS were obtained, from which the integrated pharmacokinetic parameters were calculated. The C(max) in CSF and brain tissues following IT were respectively 1.5 and 0.4-fold higher than those following IV. After IT, the AUC in CSF and brain tissues increased by 0.5 and 1.2 times compared with IV. Furthermore, the C(max) and AUC in plasma following IT were respectively 45.9% and 33.1% lower than those following IV.


CONCLUSIONS
This novel intra-cochlear administration might serve as a potential and promising alternative to TCM delivery with enhanced brain-targeted efficiency.
Department of Pharmaceutical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China. cg753@126.com
Gang
G
Chen
Lei
L
Mu
Xiao
X
Zhang
Shixiang
S
Hou
Haijun
H
Nan
D000818:Animals; D001921:Brain / Q000378:metabolism; D004333:Drug Administration Routes; D004432:Ear, Middle / Q000378:metabolism; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D006168:Guinea Pigs; D008297:Male; D008516:Medicine, Chinese Traditional; D053723:Panax notoginseng / Q000737:chemistry*; D010498:Perilymph / Q000378:metabolism; D010946:Plants, Medicinal / Q000737:chemistry; D012503:Saponins / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics
D036145:Ginsenosides; D012503:Saponins; C442759:ginsenoside Rb1; C035054:ginsenoside Rg1; C072936:notoginsenoside R1