• 四川大學(xué)華西醫(yī)院國(guó)家藥物臨床試驗(yàn)機(jī)構(gòu)·GCP中心（成都，610041）;

抗菌藥物廣泛地應(yīng)用于臨床各個(gè)科室，常常與多種藥物聯(lián)合應(yīng)用而產(chǎn)生藥物相互作用。肝微粒體細(xì)胞色素P450是藥物代謝最重要的酶系之一，藥物作用影響其活性是發(fā)生藥物相互作用的重要分子機(jī)制。了解抗菌藥物與細(xì)胞色素P450的相關(guān)關(guān)系，有助于明確藥物相互作用的分子基礎(chǔ)，有助于指導(dǎo)臨床合理聯(lián)合用藥，保障臨床治療更加安全有效。現(xiàn)就抗菌藥物與細(xì)胞色素P450的相關(guān)研究作一綜述。

引用本文： 孫家鈺,苗佳. 抗菌藥物與細(xì)胞色素P450的相關(guān)研究. 華西醫(yī)學(xué), 2012, 27(7): 982-984. doi: 復(fù)制

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1. 　茹建華, 吳伯鏞. 細(xì)胞色素P450酶與用藥選擇[J]. 醫(yī)藥導(dǎo)報(bào), 2005, 24(3): 241-242.
2. 　楊海峰, 江善祥. 苯巴比妥對(duì)雞肝微粒體CYP450活性的影響[J]. 江西農(nóng)業(yè)學(xué)報(bào), 2010, 22(5): 138-140.
3. 　毛萍, 喬定君, 馬欣榮. 細(xì)胞色素P450和醫(yī)學(xué)[J]. 中國(guó)抗生素雜志, 2011, 36(2): 93-101.
4. 　崔穎, 張永旺. P450酶的研究進(jìn)展[J]. 中國(guó)新技術(shù)新產(chǎn)品, 2009(16): 7-8.
5. 　范嵐, 彭向東, 郭志華, 等. CYP450氧化還原酶的遺傳多態(tài)對(duì)藥物代謝的影響[J]. 中國(guó)藥理學(xué)通報(bào), 2009, 25(9): 1131-1133.
6. 　陳杰, 陳孝. 細(xì)胞色素P450基因多態(tài)性對(duì)藥物療效和安全性的影響[J]. 藥品評(píng)價(jià), 2010, 7(4): 58-62.
7. 　Chen Y, Goldstein JA. The transcriptional regulation of the human CYP2C genes[J]. Curr Drug Metab, 2009, 10(6): 567-578.
8. 　徐田雪, 楊信怡, 趙昆, 等. 藥物代謝酶細(xì)胞色素P450 2D6的遺傳多態(tài)性研究進(jìn)展[J]. 中國(guó)抗生素雜志, 2009, 34(7): 385-391.
9. 　孫宜鋒, 方渡. 新型細(xì)胞色素P450氧化酶的發(fā)現(xiàn)與篩選[J]. 中國(guó)醫(yī)藥生物技術(shù), 2011, 6(3): 214-217.
10. 　張慧鋒, 王月鵬, 李妍. 細(xì)胞色素P450的研究進(jìn)展[J]. 吉林醫(yī)藥學(xué)院學(xué)報(bào), 2005, 26(3): 174-177.
11. 　Hersh EV, Moore PA. Drug interactions in dentistry: the importance of knowing your CYPs[J]. J Am Dent Assoc, 2004, 135(3): 298-311.
12. 　Chhun S, Verstuyft C, Rizzo-Padoin N, et al. Gefitinib-phenytoin interaction is not correlated with the C-erythromycin breath test in healthy male volunteers[J]. Br J Clin Pharmacol, 2009, 68(2): 226-237.
13. 　Galetin A, Gertz M, Houston JB. Contribution of intestinal cytochrome p450-mediated metabolism to drug-drug inhibition and induction interactions[J]. Drug Metab Pharmacokinet, 2010, 25(1): 28-47.
14. 　Vandenbrink BM, Isoherranen N. The role of metabolites in predicting drug-drug interactions: focus on irreversible cytochrome P450 inhibition[J]. Curr Opin Drug Discov Devel, 2010, 13(1): 66-77.
15. 　Zhang L, Wei MJ, Zhao CY, et al. Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes[J]. Acta Pharmacol Sin, 2008, 29(12): 1507-1514.
16. 　Westphal JF. Macrolide-induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin[J]. Br J Clin Pharmacol, 2000, 50(4): 285-295.
17. 　Grönlund J, Saari T, Hagelberg N, et al. Effect of telithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone[J]. J Clin Pharmacol, 2010, 50(1): 101-108.
18. 　鄒文, 周文, 歐揚(yáng). 琥乙紅霉素和阿司匹林合用對(duì)大鼠肝臟細(xì)胞色素P450酶的影響[J]. 中國(guó)醫(yī)院藥學(xué)雜志, 2008, 28(7): 505-508.
19. 　劉荔, 劉嶸, 吳暢烜, 等. 乳酸卡德沙星對(duì)大鼠肝P450酶活性的影響[J]. 中國(guó)藥科大學(xué)學(xué)報(bào), 2007, 38(2): 144-148.
20. 　Granfors MT, Backman JT, Neuvonen M, et al. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism[J]. Clin Pharmacol Ther, 2004, 76(6): 598-606.
21. 　Scholz I, Oberwittler H, Riedel KD, et al. Pharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype[J]. Br J Clin Pharmacol, 2009, 68(6): 906-915.
22. 　Shon JH, Yeo CW, Liu KH, et al. Itraconazole and rifampin alter significantly the disposition and antihistamine effect of ebastine and its metabolites in healthy participants[J]. J Clin Pharmacol, 2010, 50(2): 195-204.
23. 　Uttayamakul S, Likanonsakul S, Manosuthi W, et al. Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults[J]. AIDS Res Ther, 2010, 7: 8.
24. 　Kim SH, Kim SH, Bahn JW, et al. Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis[J]. Pharmacogenomics, 2009, 10(11): 1767-1779.
25. 　Shin KH, Kim BH, Kim TE, et al. The effects of ketoconazole and rifampicin on the pharmacokinetics of mirodenafil in healthy Korean male volunteers: an open-label, one-sequence, three-period, three-treatment crossover study[J]. Clin Ther, 2009, 31(12): 3009-3020.
26. 　Skerjanec A, Wang J, Maren K, et al. Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral Iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers[J]. J Clin Pharmacol, 2010, 50(2): 205-213.
  1. 1. 　茹建華, 吳伯鏞. 細(xì)胞色素P450酶與用藥選擇[J]. 醫(yī)藥導(dǎo)報(bào), 2005, 24(3): 241-242.
  2. 2. 　楊海峰, 江善祥. 苯巴比妥對(duì)雞肝微粒體CYP450活性的影響[J]. 江西農(nóng)業(yè)學(xué)報(bào), 2010, 22(5): 138-140.
  3. 3. 　毛萍, 喬定君, 馬欣榮. 細(xì)胞色素P450和醫(yī)學(xué)[J]. 中國(guó)抗生素雜志, 2011, 36(2): 93-101.
  4. 4. 　崔穎, 張永旺. P450酶的研究進(jìn)展[J]. 中國(guó)新技術(shù)新產(chǎn)品, 2009(16): 7-8.
  5. 5. 　范嵐, 彭向東, 郭志華, 等. CYP450氧化還原酶的遺傳多態(tài)對(duì)藥物代謝的影響[J]. 中國(guó)藥理學(xué)通報(bào), 2009, 25(9): 1131-1133.
  6. 6. 　陳杰, 陳孝. 細(xì)胞色素P450基因多態(tài)性對(duì)藥物療效和安全性的影響[J]. 藥品評(píng)價(jià), 2010, 7(4): 58-62.
  7. 7. 　Chen Y, Goldstein JA. The transcriptional regulation of the human CYP2C genes[J]. Curr Drug Metab, 2009, 10(6): 567-578.
  8. 8. 　徐田雪, 楊信怡, 趙昆, 等. 藥物代謝酶細(xì)胞色素P450 2D6的遺傳多態(tài)性研究進(jìn)展[J]. 中國(guó)抗生素雜志, 2009, 34(7): 385-391.
  9. 9. 　孫宜鋒, 方渡. 新型細(xì)胞色素P450氧化酶的發(fā)現(xiàn)與篩選[J]. 中國(guó)醫(yī)藥生物技術(shù), 2011, 6(3): 214-217.
  10. 10. 　張慧鋒, 王月鵬, 李妍. 細(xì)胞色素P450的研究進(jìn)展[J]. 吉林醫(yī)藥學(xué)院學(xué)報(bào), 2005, 26(3): 174-177.
  11. 11. 　Hersh EV, Moore PA. Drug interactions in dentistry: the importance of knowing your CYPs[J]. J Am Dent Assoc, 2004, 135(3): 298-311.
  12. 12. 　Chhun S, Verstuyft C, Rizzo-Padoin N, et al. Gefitinib-phenytoin interaction is not correlated with the C-erythromycin breath test in healthy male volunteers[J]. Br J Clin Pharmacol, 2009, 68(2): 226-237.
  13. 13. 　Galetin A, Gertz M, Houston JB. Contribution of intestinal cytochrome p450-mediated metabolism to drug-drug inhibition and induction interactions[J]. Drug Metab Pharmacokinet, 2010, 25(1): 28-47.
  14. 14. 　Vandenbrink BM, Isoherranen N. The role of metabolites in predicting drug-drug interactions: focus on irreversible cytochrome P450 inhibition[J]. Curr Opin Drug Discov Devel, 2010, 13(1): 66-77.
  15. 15. 　Zhang L, Wei MJ, Zhao CY, et al. Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes[J]. Acta Pharmacol Sin, 2008, 29(12): 1507-1514.
  16. 16. 　Westphal JF. Macrolide-induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin and dirithromycin[J]. Br J Clin Pharmacol, 2000, 50(4): 285-295.
  17. 17. 　Grönlund J, Saari T, Hagelberg N, et al. Effect of telithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone[J]. J Clin Pharmacol, 2010, 50(1): 101-108.
  18. 18. 　鄒文, 周文, 歐揚(yáng). 琥乙紅霉素和阿司匹林合用對(duì)大鼠肝臟細(xì)胞色素P450酶的影響[J]. 中國(guó)醫(yī)院藥學(xué)雜志, 2008, 28(7): 505-508.
  19. 19. 　劉荔, 劉嶸, 吳暢烜, 等. 乳酸卡德沙星對(duì)大鼠肝P450酶活性的影響[J]. 中國(guó)藥科大學(xué)學(xué)報(bào), 2007, 38(2): 144-148.
  20. 20. 　Granfors MT, Backman JT, Neuvonen M, et al. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism[J]. Clin Pharmacol Ther, 2004, 76(6): 598-606.
  21. 21. 　Scholz I, Oberwittler H, Riedel KD, et al. Pharmacokinetics, metabolism and bioavailability of the triazole antifungal agent voriconazole in relation to CYP2C19 genotype[J]. Br J Clin Pharmacol, 2009, 68(6): 906-915.
  22. 22. 　Shon JH, Yeo CW, Liu KH, et al. Itraconazole and rifampin alter significantly the disposition and antihistamine effect of ebastine and its metabolites in healthy participants[J]. J Clin Pharmacol, 2010, 50(2): 195-204.
  23. 23. 　Uttayamakul S, Likanonsakul S, Manosuthi W, et al. Effects of CYP2B6 G516T polymorphisms on plasma efavirenz and nevirapine levels when co-administered with rifampicin in HIV/TB co-infected Thai adults[J]. AIDS Res Ther, 2010, 7: 8.
  24. 24. 　Kim SH, Kim SH, Bahn JW, et al. Genetic polymorphisms of drug-metabolizing enzymes and anti-TB drug-induced hepatitis[J]. Pharmacogenomics, 2009, 10(11): 1767-1779.
  25. 25. 　Shin KH, Kim BH, Kim TE, et al. The effects of ketoconazole and rifampicin on the pharmacokinetics of mirodenafil in healthy Korean male volunteers: an open-label, one-sequence, three-period, three-treatment crossover study[J]. Clin Ther, 2009, 31(12): 3009-3020.
  26. 26. 　Skerjanec A, Wang J, Maren K, et al. Investigation of the pharmacokinetic interactions of deferasirox, a once-daily oral Iron chelator, with midazolam, rifampin, and repaglinide in healthy volunteers[J]. J Clin Pharmacol, 2010, 50(2): 205-213.