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  • Title: Brain pharmacokinetics of tetramethylpyrazine after intranasal and intravenous administration in awake rats.
    Author: Feng J, Li F, Zhao Y, Feng Y, Abe Y.
    Journal: Int J Pharm; 2009 Jun 22; 375(1-2):55-60. PubMed ID: 19481691.
    Abstract:
    Brain pharmacokinetic behaviors of tetramethylpyrazine (TMP) following intranasal (i.n.) and intravenous (i.v.) administration, have been investigated using brain microdialysis technique in free-moving rats. A cross-over design was employed in the present experiment. The same set of rats (n=5) received i.v. injection at a dose of 10 mg/kg TMP via tail vein. Equal dose was administered intranasally. After application, the dialysates sampled from the left striatum were measured by HPLC-UV detection. The results indicated that the mean corrected TMP concentration of 1.49 microg/ml was obtained at 5 min following i.n. dosing while no TMP in the dialysate sampled 5 min after i.v. injection was detected, in the range of our measurement limit. No compartment model was most suitable for analysis of the concentration vs. time results after i.n. dosing. Thus, a non-compartment model was used in the analysis of all experimental data. No significant differences in brain pharmacokinetic parameters, except Cmax, were found between both i.n. and i.v. administration routes. AUCi.n./AUCi.v. ratio was 92.42%. Finally, compared with i.v. application, intranasal administration of TMP could obtain significantly fast absorption from nasal to ipsilateral striatum and equal bioavailability. Therapeutically relevant nasal formulation is a potential alternative for intravenous administration approach for TMP.
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