Interindividual variability of once-daily ritonavir boosted saquinavir pharmacokinetics in Thai and UK patients
Interindividual variability of once-daily ritonavir boosted saquinavir pharmacokinetics in Thai and UK patients
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DOI：
10.1093/jac/dki354
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发表时间：
2005-11-01
影响因子：
5.2
通讯作者：
Burger, DM
中科院分区：
文献类型：
--
作者：
Autar, RS;Boffito, M;Burger, DM
目的：不同的沙奎那韦/利托那韦暴露可能导致治疗失败。目的：确定影响沙奎那韦/利托那韦血药浓度变异性的因素。方法：收集来自泰国和英国的45例患者的沙奎那韦/利托那韦数据，剂量为1600/100 mg/天，来自三个独立的药动学研究。药动学参数以非室分析为基础。以沙奎那韦为因变量，利托那韦曲线下面积(AUC)、性别、体重、体重指数(BMI)和研究地点为自变量进行单因素分析。结果：泰国患者的沙奎那韦AUC、最大血药浓度(C-max)和最小血药浓度(C-min)高于英国患者。单因素分析显示体重、性别、研究地点与利托那韦和沙奎那韦的AUC有关(P<；0.05)，而BMI(P=0.13)与利托那韦和沙奎那韦的AUC无关。在多因素分析中，利托那韦AUC(P=0.0001)和研究地点(P=0.0021)与沙奎那韦AUC显著相关(R2=0.5)。结论：利托那韦AUC和研究地点可能与沙奎那韦暴露有关。研究地点应被视为分析研究之间国家和研究具体差异的总和--例如生活方式、环境、遗传背景和饮食结构的差异。
Objectives: Differential exposure to saquinavir/ritonavir may lead to therapy failure. The objective was to identify factors that influence variability of saquinavir/ritonavir plasma concentrations.Methods: Saquinavir/ritonavir data, dosed as 1600/100 mg once daily, from three separate pharmacokinetic studies, in 45 patients from Thailand and the UK, were pooled. Pharmacokinetic parameters were based on non-compartmental analysis. Univariate analysis was performed with saquinavir as the dependent variable, and ritonavir area under the curve (AUC), gender, body weight, body mass index (BMI) and study site as independent variables. Variables with a P value < 0.10 were included in a multivariate linear regression analysis.Results: Higher saquinavir AUCs, maximum concentrations (C-max) and minimum concentrations (C-min) were seen in Thai patients than in UK patients. Univariate analysis showed associations between body weight, gender, study site and ritonavir AUC and saquinavir AUC (P < 0.05), whereas BMI (P = 0.13) did not. In the multivariate analysis, ritonavir AUC (P = 0.0001) and study site (P = 0.0021) were significantly related to saquinavir AUC (R-2 = 0.50).Conclusions: The ritonavir AUC and study site appeared to be related to exposure of saquinavir. Study site should be viewed as the total of country- and study-specific differences-such as differences in lifestyle, environment, genetic background and dietary composition-between the analysed studies.