title: Brain microdialysate, CSF and plasma pharmacokinetics of ligustrazine hydrochloride in rats after intranasal and intravenous administration.
abstract: The aim of this work was to investigate the pharmacokinetics of ligustrazine hydrochloride (LZH) in plasma, cerebrospinal fluid (CSF) and cerebral cortex after intranasal (10 mg/kg) or intravenous administration (10 mg/kg) in male Sprague-Dawley rats. Plasma, CSF and cerebral cortex microdialysates were collected at timed intervals for the measurement of LZH by a quick and sensitive HPLC-UV method. LZH entered the brain quickly following both routes of administration. No significant difference was observed between the AUCCSF or cortex /AUCplasma ratio of LZH after intranasal administration (38.4%, 17.4%) and that after intravenous injection (45.9%, 19.9%). The drug targeting index (DTI) was 0.85 and 0.91 in the CSF and cortex, respectively. In conclusion, LZH is rapidly absorbed into the systemic circulation following intranasal administration. There is no direct pathway for LZH transport from the nasal cavity to the brain. The rapidity and magnitude of LZH penetration into the brain indicate that intranasal administration of this agent is a promising alternative to intravenous administration.
authors.affiliation: Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, 310013, PR China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhan
authors.initials: Z
authors.lastname: Tang
authors.forename: Wanggang
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001921:Brain / Q000378:metabolism*; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D011719:Pyrazines / Q000008:administration & dosage / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D011719:Pyrazines; C017953:tetramethylpyrazine
keywords: cerebrospinal fluid; intranasal administration; ligustrazine hydrochloride; microdialysis; pharmacokinetics; plasma