本文關(guān)鍵詞： HIV-1 洛匹那韋 藥代動力學 依從性 TDM　出處：《北京協(xié)和醫(yī)學院》2014年碩士論文　論文類型：學位論文

【摘要】：研究目的觀察中國HIV/AIDS患者服用洛匹那韋/利托那韋復(fù)合制劑(克立芝@)達穩(wěn)態(tài)后洛匹那韋的臨床藥代動力學特點；通過測定HIV感染者血漿中洛匹那韋濃度,探討患者長期服藥依從性與病毒學治療效果的關(guān)系。研究方法招募接受包含洛匹那韋/利托那韋復(fù)合制劑抗病毒治療方案長期隨訪的16位患者,于服藥前及服藥后至12h采集靜脈血,應(yīng)用高效液相色譜法檢測人血漿中洛匹那韋濃度,應(yīng)用WinNonlin軟件進行藥動學參數(shù)計算。選取服用國家免費治療二線方案(TDF+3TC+LPV/r)并規(guī)律隨訪96周的患者84例,測定每次隨訪點血漿中VL及LPV濃度,分析LPV濃度與病毒學療效的關(guān)系。研究結(jié)果非房室模型分析顯示,洛匹那韋PK參數(shù)分別為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組和AZT組中LPV達峰時間(Tmax)分別為4.01±0.43h和3.38±0.52h(p=0.048)；LPV藥-時曲線下面積AUClast分別為64.44±27.25和75.32±19.48(μg*h/mL)(P=0.024)；AUCINF分別為109.92±26.43和 137.68±37.79(μg*h/mL)(p=0.028).84例入組患者中,病毒學失敗組(VF)11例,病毒學應(yīng)答組(VS)73例。病毒學應(yīng)答組中,VL在治療24周后低于檢測下限,治療第4周及之后的各隨訪點的平均LPV谷濃度均高于1.0μ g/ml；病毒學失敗組中,72.7%的患者出現(xiàn)LPV濃度為0μg/ml,提示依從性不良；共17例患者在隨訪中曾經(jīng)出現(xiàn)LPV濃度低于1.0 μ g/ml的情況,低血藥濃度的發(fā)生率與VF呈正相關(guān)(r2=0.9418),當發(fā)生率≤10%時,只有4.5%的患者出現(xiàn)病毒學失敗。結(jié)論洛匹那韋達穩(wěn)態(tài)的HIV-1感染患者血漿Cmin低于國外研究報道,Tmax、Cmax、 AUC0-24、T1/2、CL/F與國外研究報道類似。LPV與TDF聯(lián)用時,其達峰時間晚于AZT組,生物利用度低于AZT組。規(guī)律服藥時,LPV谷濃度略高于LPV的最低有效濃度,臨床應(yīng)予以加強患者規(guī)律服藥的依從性教育。監(jiān)測長期服藥患者的血藥濃度,是判斷服藥依從性的簡便方法。服藥依從性良好的患者,其血漿LPV谷濃度均高于1.0 μg/ml,病毒學失敗可能與依從性不良有關(guān)。低血藥濃度的發(fā)生率與病毒學失敗呈正相關(guān)。
[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 鹵0.23 h, C max10.36 鹵3.42 渭 g 路mL 路min 2.18 鹵0.3.4 渭 g / mL, respectively. AUC0-24 116.22 鹵15.68 渭 g / mL T 1 / 2 4.5 鹵0.13 h. The peak time of LPV in CL/F3.44 鹵1.34L / h 路TDF group and AZT group was 4.01 鹵0.43h and 3.38 鹵0.52h, respectively. (2) p0. 048; The area under the curve of LPV was 64.44 鹵27.25 and 75.32 鹵19.48, respectively. AUCINF was 109.92 鹵26.43 and 137.68 鹵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.
【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R512.91

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本文編號：1489605