Pharmacokinetics of once-daily saquinavir hard-gelatin capsules and Saquinavir soft-gelatin capsules boosted with Ritonavir in HIV-1-infected subjects
Pharmacokinetics of once-daily saquinavir hard-gelatin capsules and Saquinavir soft-gelatin capsules boosted with Ritonavir in HIV-1-infected subjects
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DOI：
10.1097/00126334-200304010-00005
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发表时间：
2003-04-01
影响因子：
3.6
通讯作者：
Phanuphak, P
中科院分区：
文献类型：
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作者：
Cardiello, PG;Monhaphol, T;Phanuphak, P
目的：研究沙奎那韦（SQV）硬明胶胶囊（HGC）/利托那韦（RTV）1600/100 mg每日一次与SQV软明胶胶囊（SGC）/RTV 1600/100 mg每日一次相比的药代动力学。我们评估了13名随机选择的HIV-1感染受试者，他们每天服用一次SQV SGC/RTV，1600/100 mg，联合双核苷逆转录酶抑制剂（NRTI）。受试者接受1周SQV HGC/RTV和NRTI治疗，随后进行稳态SQV PK测定。然后受试者改为SQV SGC/RTV和NRTI治疗1周，然后再次进行稳态SQV PK测定。计算血浆浓度-时间曲线下面积（AUC）、最大浓度（C-max）、最小浓度（C-min）、至C-max的时间和消除半衰期。HGC和SGCs之间的AUC值无显著差异，中位数（加上四分位数范围[IQR]）分别为50.0（42.6-71.5）和35.5（28.0-50.2）mg/L/h（p = 0.056）。受试者间变异性导致SQV SGC组13例受试者中的4例和SQV HGC组13例受试者中的2例的C min低于最低有效浓度0.05 mg/L。结论：每日一次SQV HGC，1600 mg，用每日一次RTV，100 mg加强，导致PK参数与1600 mg SQV SGC/100 mg RTV每日一次观察到的PK参数相似。每日一次SQV HGC/RTV，1600/100 mg，可能更容易在发展中国家使用，并可能增加药物成本较低，胶囊尺寸较小，对冷藏的需求减少的地方。
Objective: To investigate the pharmacokinetics of once-daily saquinavir (SQV) hard-gelatin capsule (HGC)/ritonavir (RTV), 1600/100 mg, compared with once-daily SQV soft-gelatin capsule (SGC)/RTV, 1600/100 mg.Methods: We evaluated 13 randomly selected HIV-1-infected subjects taking once-daily SQV SGC/RTV, 1600/100 mg, plus dual nucleoside reverse transcriptase inhibitors (NRTIs) in this pharmacokinetic (PK) substudy. Subjects took 1 week of SQV HGC/RTV and NRTIs, followed by steady-state SQV PK determinations. Subjects then changed to SQV SGC/RTV and NRTIs for 1 week, followed again by steady-state SQV PK determinations. Area under the plasma concentration versus time curve (AUC), maximum concentration (C-max), minimum concentration (C-min), time to C-max, and elimination half-life were calculated.Results: There was no significant difference in AUC values between HGCs and SGCs, with a median (plus interquartile range [IQR]) of 50.0 (42.6-71.5) versus 35.5 (28.0-50.2) mg/L/h, respectively (p = .056). Intersubject variability resulted in 4 of 13 subjects on the SQV SGCs and 2 of 13 subjects on the SQV HGCs having a C-min. below the minimum effective concentration of 0.05 mg/L.Conclusion: Once-daily SQV HGCs, 1600 mg, boosted with once-daily RTV, 100 mg, resulted in PK parameters that were similar to those observed with 1600 mg of SQV SGC/100 mg RTV once daily. Once-daily SQV HGC/RTV, 1600/100 mg, may be easier to use in developing countries and may increase access where drug costs can be less, the capsule size is smaller, and the need for refrigeration is lessened.