洛匹那韦在中国成人HIV-1感染者体内的药动学和药效学研究

发布时间：2018-02-04 06:38

本文关键词： HIV-1 洛匹那韦药代动力学依从性 TDM　出处：《北京协和医学院》2014年硕士论文　论文类型：学位论文

【摘要】：研究目的观察中国HIV/AIDS患者服用洛匹那韦/利托那韦复合制剂(克立芝@)达稳态后洛匹那韦的临床药代动力学特点；通过测定HIV感染者血浆中洛匹那韦浓度,探讨患者长期服药依从性与病毒学治疗效果的关系。研究方法招募接受包含洛匹那韦/利托那韦复合制剂抗病毒治疗方案长期随访的16位患者,于服药前及服药后至12h采集静脉血,应用高效液相色谱法检测人血浆中洛匹那韦浓度,应用WinNonlin软件进行药动学参数计算。选取服用国家免费治疗二线方案(TDF+3TC+LPV/r)并规律随访96周的患者84例,测定每次随访点血浆中VL及LPV浓度,分析LPV浓度与病毒学疗效的关系。研究结果非房室模型分析显示,洛匹那韦PK参数分别为Tmax3.88±0.23h,Cmax10.36±3.42 μg/mL,Gmin 2.18±03.4 μg/mL,AUC0-24 116.22±15.68 μg*h/mL,T1/2 4.5±0.13h,CL/F3.44±1.34 L/h。TDF组和AZT组中LPV达峰时间(Tmax)分别为4.01±0.43h和3.38±0.52h(p=0.048)；LPV药-时曲线下面积AUClast分别为64.44±27.25和75.32±19.48(μg*h/mL)(P=0.024)；AUCINF分别为109.92±26.43和 137.68±37.79(μg*h/mL)(p=0.028).84例入组患者中,病毒学失败组(VF)11例,病毒学应答组(VS)73例。病毒学应答组中,VL在治疗24周后低于检测下限,治疗第4周及之后的各随访点的平均LPV谷浓度均高于1.0μ g/ml；病毒学失败组中,72.7%的患者出现LPV浓度为0μg/ml,提示依从性不良；共17例患者在随访中曾经出现LPV浓度低于1.0 μ g/ml的情况,低血药浓度的发生率与VF呈正相关(r2=0.9418),当发生率≤10%时,只有4.5%的患者出现病毒学失败。结论洛匹那韦达稳态的HIV-1感染患者血浆Cmin低于国外研究报道,Tmax、Cmax、 AUC0-24、T1/2、CL/F与国外研究报道类似。LPV与TDF联用时,其达峰时间晚于AZT组,生物利用度低于AZT组。规律服药时,LPV谷浓度略高于LPV的最低有效浓度,临床应予以加强患者规律服药的依从性教育。监测长期服药患者的血药浓度,是判断服药依从性的简便方法。服药依从性良好的患者,其血浆LPV谷浓度均高于1.0 μg/ml,病毒学失败可能与依从性不良有关。低血药浓度的发生率与病毒学失败呈正相关。
[Abstract]:Objective to observe the clinical pharmacokinetic characteristics of ropinavir / ritonavir in Chinese patients with HIV/AIDS. The concentration of lopinavir in plasma of HIV infected patients was determined. To explore the relationship between long-term compliance and virological efficacy. Methods 16 patients were recruited for long-term follow-up with the combination of Lopinavir and Ritonavir. Venous blood was collected before and 12 hours after taking the drug, and the concentration of lopinavir in human plasma was determined by HPLC. The pharmacokinetic parameters were calculated by WinNonlin software. 84 patients who were given TDF3TC LPV-r) were selected and followed up regularly for 96 weeks. Plasma VL and LPV concentrations were measured at each follow-up point, and the relationship between LPV concentration and virological efficacy was analyzed. The competition parameters of Lopinavir were Tmax3.88 卤0.23 h, C max10.36 卤3.42 渭 g 路mL 路min 2.18 卤0.3.4 渭 g / mL, respectively. AUC0-24 116.22 卤15.68 渭 g / mL T 1 / 2 4.5 卤0.13 h. The peak time of LPV in CL/F3.44 卤1.34L / h 路TDF group and AZT group was 4.01 卤0.43h and 3.38 卤0.52h, respectively. (2) p0. 048; The area under the curve of LPV was 64.44 卤27.25 and 75.32 卤19.48, respectively. AUCINF was 109.92 卤26.43 and 137.68 卤37.79, respectively. There were 11 cases of virology failure group and 73 cases of virological response group. In virology response group, VL was lower than the detection limit after 24 weeks of treatment. The mean LPV valley concentration was higher than 1.0 渭 g / ml at 4 weeks and after treatment. In the virological failure group, 72.7% of the patients had LPV concentration of 0 渭 g / ml, indicating poor compliance. A total of 17 patients were followed up with LPV below 1.0 渭 g / ml. The incidence of low blood drug concentration was positively correlated with VF (r _ 2r _ 2r _ (0.9418)). When the incidence was less than 10%, only 4.5% patients had virology failure. Conclusion the plasma Cmin of patients with stable HIV-1 infection of Lopinavida is lower than that of foreign studies. The peak time of Cmax, AUC0-24T1 / 2C / F in combination with TDF was later than that in AZT group. The bioavailability was lower than that in AZT group. The valley concentration of LPV was a little higher than the minimum effective concentration of LPV. Clinical practice should strengthen compliance education of patients with regular medication. Monitoring the blood drug concentration of long-term patients is a simple method to judge drug compliance. Patients with good drug compliance. The concentrations of plasma LPV were higher than 1.0 渭 g / ml, virological failure may be related to poor compliance, and the incidence of low blood drug concentration was positively correlated with the failure of virology.
【学位授予单位】：北京协和医学院
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R512.91

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