OBJECTIVE To study the pharmacokinetics of nasal tetramethylpyrazine phosphate (TMPP) pH-sensitive in situ gel in rat blood and brain. METHODS After intranasal administration of TMPP pH-sensitive in situ gel and TMPP solution respectively in rats, microdialysis was used to collect brain and blood samples simultaneously. The concentration of TMPP in the sample was measured by HPLC. Main pharmacokinetic parameters were calculated by Kinetica 4.4 pharmacokinetic software. RESULTS The concentration-time curves of the two preparations fitted to two-compartment model. The main pharmacokinetic parameters of TMPP pH-sensitive in situ gel and TMPP solution in blood and in brain were as follows: in blood: tmax (15.0±1.0) and (35.0±1.0) min; ρmax(5.857±1.3)and(5.848±1.0)μg·mL-1;AUC0~∞(529.9±68.6) and (642.7±54.3) μg·mL·min-1, respectively. In brain: tmax (15.0±1.0) and (35.0±1.0) min; ρmax(7.134±0.8)and(6.738±1.1)μg·mL-1;AUC0~∞(615.4±71.2) and (801.4±67.5)μg·mL·min-1, respectively. CONCLUSION TMPP in the pH-sensitive in situ gel can be easily absorbed and transferred into brain after intranasal administration, and the gel shows sustained-release effect.
Key words
tetramethylpyrazine phosphate /
pH-sensitive in situ gel /
intranasal administration /
microdialysis /
pharmacokinetics
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References
[1] WEI G, XU H, ZHENG J M. The forming mechanism of in situ gel and its appliance in drug controlling and delivering fields [J]. Chin Pharm J(中国药学杂志),2003, 38 (8): 564-568.
[2] TSAI T H, LIANG C C. Pharmacokinetics of tetramethylpyrazine in rat blood and brain using microdialysis [J]. Int J Pharm, 2001, 216: 61-66.
[3] CUI H Z, LIU F Q, WANG Y P, et al. Studies of preparation and in vitro absorption of ginkgo biloba leaf in-situ nasal gel[J]. J Pharm Pract, 2010, 28 (2): 118-121.
[4] WU Z E, WANG D Q. Application of sites-microdialysis technology in pharmacokinetic studies[J].China J Chin Mater Med(中国中药杂志), 2010, 35(13):1765-1768.
[5] YAN Y L, YE Y, ZHOU L L. Study on brain pharmacokinetics of tetramethylpyrazine phosphate after intranasal administration[J]. Tradit Chin Drug Res Clin Pharmacol(中药新药与临床药理), 2009,20(6):548-550.
[6] LI F Z, FENG J. Brain microdialysis technology and its application in brain pharmacokinetics[J]. Chin Pharm J(中国药学杂志), 2006, 41 (6): 405-407.
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Footnotes
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