P-糖蛋白表达对晚期癌痛病人吗啡或丁丙诺啡镇痛效果的影响

目的 评价P-糖蛋白(P-gp)表达对晚期癌痛病人吗啡或丁丙诺啡镇痛效果的影响.方法 晚期癌痛病人150例,其中50例肿瘤组织P-gp表达阴性病人随机分为2组(n=25):M1组和B1组,100例肿瘤组织P-gp表达阳性病人随机分为4组(n=25):M2组、M3组、B2组和B3组.各组静脉注射负荷量后进行PCIA,M1组、M2组和M3组负荷量为吗啡2.5 mg,B1组、B2组和B3组负荷量为丁丙诺啡0.15 mg,各组PCIA时药物配方分别为:M1组和M2组吗啡35 mg+氟哌利多5mg,M3组吗啡55 mg+氟哌利多5 mg;B1组和B2组丁丙诺啡0.9 mg+氟哌利多5 mg,B3组丁丙诺啡1.5 mg+氟哌利多5 mg,所用药物均用生理盐水稀释至100 ml,背景输注速率2 ml/h,PCA量0.5 ml,锁定时间15 min.分别于镇痛开始时、4、12、24、48 h时进行VAS评分,分别于镇痛4、12、24、48 h时采集静脉血样,检测血药浓度.结果 M1组和M3组VAS评分低于M2组,M3组血药浓度高于M1组和M2组(P＜0.05);B1组和B3组VAS评分低于B2组,B3组血药浓度高于B1组和B2组(P＜0.05);M1组与M2组间及B1组与B2组比较血药浓度差异无统计学意义(P＞0.05).结论 P-gp表达阳性可减弱晚期癌痛病人吗啡或丁丙诺啡的镇痛效果.

Effect of expression of P-glycoprotein in tumor tissue on analgesic efficacy of morphine and buprenorphine in advanced cancer patients with pain

Objective To evaluate the effect of the expression of P-glycoprotein (P-gp) in tumor tissue on analgesic efficacy of morphine and buprenorphine in advanced cancer patients with pain. Methods One hundred and fifty advanced cancer patients with pain aged 51-64 yr weighing 54-65 kg were included in this study. The expression of P-gp was negative in the tumor tissue in 50 patients (group M1 and B1, n = 25 each) and positive in 100 patients (group M2 ,M3 ,and B2 ,B3, n =25 each). The PCA regimen for the 6 groups were listed in the table .Pain was assessed with VAS scores (0 = no pain, 10 = worst pain) and venous blood samples were taken for determination of blood morphine/buprenorphine concentrations at 4, 12, 24 and 48 h of PCIA. Results The six groups were comparable with respect to age, body weight, M/F sex ratio, types of cancer, baseline pain level and education. The analgesic efficacy of morphine and buprenorphine was better ( VAS scores were significantly lower)in P-gp expression negative patients (group M1 and B1 ) than in P-gp expression positive patients (group M2 and B2 ). Higher doses of morphine and buprenorphine provided better analgesic efficacy in P-gp expression positive patients in group M3 and B3 than in group M2 and B2. Plasma morphine and buprenorphine concentrations were comparable between group M1 , B1 and M2, B2 and were significantly higher in group M3 and B3 at each time point. Conclusion Positive P-gp expression in the tumor tissue can decrease the analgesic efficacy of morphine and buprenorphine in advanced cancer patients with pain.