Influence of Caffeine on the Sedative Effects of Promethazine Based on Pharmacokinetics and Metabolomics

doi:10.7503/cjcu20120702

Abstract

Abstract:

Pharmacokinetic and metabolomic methods were employed to investigate the influence of caffeine on the sedative effects of promethazine. First, a space flight vigilance tasks simulation system and Standford sleepiness scale(SSS) were used to compare the effect of single administration of promethazine and combination administration with caffeine on the cognitive function of volunteers. Then software named Kinetica was used to calculate some of the important pharmacokinetic parameters of promethazine before and after the combination. And the possible influencing factors were discussed. Finally, a metabolomic method was applied to identify the potential biomarkers between two groups. The results suggest that caffeine could confront the sedative effects of promethazine and so improve the decreased cognitive function, which might be induced by the accelerated metabolism of promethazine and the altered dopamine, norepinephrine and epinephrine related pathways. This study provides a new approach for the research of combination administration of promethazine and caffeine.

Key words: Caffeine, Promethazine, Sedative effects, Pharmacokinetics, Metabolomics

CLC Number:

O657

TrendMD:

HUANG Min, GAO Jian-Yi, ZHAI Zhi-Gang, LIANG Qiong-Lin, WANG Yi-Ming, BAI Yan-Qiang, LUO Guo-An. Influence of Caffeine on the Sedative Effects of Promethazine Based on Pharmacokinetics and Metabolomics[J]. Chem. J. Chinese Universities, 2013, 34(4): 829.

References

[1] Shupak A., Gordon C. R., Aviat. Space Environ. Med., 2006, 77(12), 1213—1223

[2] Mahdy A. M., Webster N. R., Anaesth. Intens. Care Med., 2011, 12(7), 324—329

[3] Hindmarch I., Shamsi Z., Stanley N., Fairweather D. B., Br. J. Clin. Pharmacol., 1999, 48(2), 200—206

[4] Estrada A., le Duc P. A., Curry I. P., Phelps S. E., Fuller D. R., Aviat. Space Environ. Med., 2007, 78(4), 408—413

[5] Vlase L., Popa A., Neag M., Muntean D., Bldea I., Leucu ??塅 a S. E., J. Clin. Pharmacol., 2011, 51(8), 1233—1236

[6] Zhang C., Wang L., Guan X., Fawcett J. P., Zhao L., Sun Y., Gu J., Chem. Res. Chinese Universities, 2010, 26(6), 910—914

[7] Wang Y., Jiang Z. T., Liang Q. L., Wang Y. M., Wang M., Luo G. A., Chem. J. Chinese Universities, 2010, 31(1), 57—60(王勇, 江芝婷, 梁琼麟, 王义明, 王梅, 罗国安. 高等学校化学学报, 2010, 31(1), 57—60)

[8] Liang X. P., Zhang Z., Hu P., Zhong H. F., Ge Z. H., Zou T. T., Liang Q. L., Wang Y. M., Luo G. A., Chem. J. Chinese Universities,2011, 32(1), 38—43(梁晓萍, 张政, 胡坪, 钟宏福, 葛朝晖, 邹婷婷, 梁琼麟, 王义明, 罗国安. 高等学校化学学报, 2011, 32(1), 38—43)

[9] Chen Y. H., Zhang R. P., Song Y. M., Dong L. J., Zhan Q. M., Abliz Z., Chin. J. Anal. Chem., 2011, 39(2), 173—177(陈艳华, 张瑞萍, 宋咏梅, 董立佳, 詹启敏, 再帕尔·阿不力孜. 分析化学, 2011, 39(2), 173—177)

[10] Li X. J., Wen Z. H., Hu W. D., Zhou C. D., Chin. Med. Equipment J., 2004, (9), 24—25(李晓京, 文治洪, 胡文东, 周传岱. 医疗卫生装备, 2004, (9), 24—25)

[11] Nuotto E., Eur. J. Clin. Pharmacol., 1983, 24(5), 603—609

[12] Huang M., Gao J. Y., Zhai Z. G., Liang Q. L., Wang Y. M., Bai Y. Q., Luo G. A., J. Pharm. Biomed. Anal., 2012, 62, 119—128

[13] Li L., Metabonomics Study and Applications on Diseases and Drug Intervention, Shanghai: East China University of Science and Technology, 2010(黎莉. 疾病及药物干预的代谢组学方法及应用研究, 上海: 华东理工大学, 2010)

[14] Misangyi V. F., le Pine J. A., Algina J., Jr Goeddeke F., Organ. Res. Methods, 2009, 9(1), 5—28

[15] Girden E. R., ANOVA: Repeated Measures, Newbury Park, Sage, 1992

[16] Song Q., Putcha L., J. Chromatogr. B Biomed. Sci. Appl., 2001, 763(1/2), 9—20

[17] Taylor G., Houston J. B., Shaffer J., Mawer G., Br. J. Clin. Pharmacol., 1983, 15(3), 287—293

[18] University of Lausanne, Pharmacokinetics: Chapter 2, Pharmacokinetic Parameters: Hepatic Clearance, [2012-07-16]. http://sepia.unil.ch/pharmacology/index.php?id=64

[19] Bates G. D. L., Lopes O., van Woerkom A. E., Klovrza L., Waring R., Acta Psychiatr. Scand., 1999, 99(4), 294—299

[20] Kanehisa Laboratories, Tyrosine Metabolism-Homo Sapiens(human), [2012-07-16]. http://www.genome.jp/dbget-bin/get_pathway?org_name=hsa&mapno=map00350

[21] Dong W. X., Ni X. L., Acta Pharmacol. Sin., 2002, 23(1), 59—65

[22] Strenkoski-Nix L. C., Ermer J., DeCleene S., Cevallos W., Mayer P. R., Am. J. Health Syst. Pharm., 2000, 57(16), 1499—1505

[23] Kavanagh J. J., Grant G. D., Anoopkumar-Dukie S., Clin. Neurophysiol., 2012, 123(4), 780—786

[24] Garrett B. E., Griffiths R. R., Pharmacol. Biochem. Behav., 1997, 57(3), 533—541

[25] Ferre S., J. Alzheimers Dis., 2010, 20(Suppl.1), S35—S49