Pharmacokinetics of a New Tetramethylpyrazine Analogue CXC195 in Rats

Abstract

Objective:

To investigate the pharmacokinetical characteristics of a new neuroprotective drug CXC195 after intraperitoneal injection in rats.

Method:

A single 10 mg · kg⁻¹ of CXC195 was intraperitoneally injected to 8 rats after fasting overnight, respectively. 500 microliters of blood samples were collected at scheduled time before and after administration. CXC195 in rats’ plasma was separated on a Diamonsil C₁₈ column (150 mm×4.6 mm, 5 μm), eluted using methanol − 0.05 mM NaH₂PO₄ solution (86:14, v/v) as mobile phase, and detected by UV detector at wavelength of 278 nm. The plasma concentration of CXC195 was determined by established HPLC method after disposition and its pharmacokinetic parameters were analyzed and evaluated by Drug and Statistic (version 2.0).

Results:

The Cmax, T_max, t_1/2, AUC_0-8, AUC_0-∞, MRT_0-8, MRT_0-∞, CL/F and V/F of CXC195 after­single dose intraperitoneal injection of 10 mg · kg⁻¹ CXC195 were 12.37±5.35 μg · mL⁻¹, 0.5±0.21 h,4.24±2.43 h, 24.89±8.32 μg · mL⁻¹ · h, 28.57±9.66 μg · mL⁻¹ · h, 2.00±0.53 h, 2.93±0.75 h, 1.4±0.73 L · h⁻¹ and 1.16±0.68 L.

Conclusion:

The established HPLC method was sensitive, rapid, and suitable for CXC195 pharmacokinetic study. The procedure of CXC195 in rat was fit to double-compartmental model with lag time of 0.13 h.

Key words

CXC195 - tetramethylpyrazine - pharmacokinetics - HPLC

*

^* These authors contributed equally to this work.

• References

• 1 Jia J, Zhang X, Hu YS et al. Protective effect of tetraethyl pyrazine against focal cerebral ischemia/reperfusion injury in rats: therapeutic time window and its mechanism. Thromb Res 2009; 123: 727-730
• 2 Kao TK, Ou YC, Kuo JS et al. Neuroprotection by tetramethylpyrazine against ischemic brain injury in rats. Neurochem Int 2006; 48: 166-176
• 3 Liao SL, Kao TK, Chen WY et al. Tetramethylpyrazine reduces ischemic brain injury in rats. Neurosci Lett 2004; 372: 40-45
• 4 Cheng XC, Liu XY, Xu WF et al. Design, synthesis, and biological activities of novel Ligustrazine derivatives. Bioorg Med Chem 2007; 15: 3315-3320
• 5 Ou Y, Dong X, Liu XY et al. Mechanism of tetramethylpyrazine analogue CXC195 inhibition of hydrogen peroxide-induced apoptosis in human endothelial cells. Biol Pharm Bull 2010; 33: 432-438
• 6 Guidance for Industry: Bioanalytical Method Validation . US Department of Health and Human Services, FDA, CDER and CVM. 2001