Boffito Marta, Maitland Desmond, Dickinson Laura, Back David, Hill Andrew, Fletcher Carl, Moyle Graeme, Nelson Mark, Gazzard Brian, Pozniak Anton
PK Research Ltd, St Stephen's Centre, Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH, UK.
J Antimicrob Chemother. 2005 Apr;55(4):542-5. doi: 10.1093/jac/dki043. Epub 2005 Feb 18.
The amount of ritonavir needed to enhance saquinavir hard gel (hg) plasma concentrations is unclear. Reduced ritonavir dosing may help to reduce ritonavir-related side effects and costs. This study examined the pharmacokinetics of twice-daily saquinavir-hg (1000 mg) in the presence of ritonavir 100 mg, dosed twice-daily and once-daily on one single occasion.
Eighteen HIV-infected adults taking saquinavir/ritonavir 1000/100 mg twice-daily underwent pharmacokinetic (PK) assessment of saquinavir/ritonavir on day 1 following a morning saquinavir/ritonavir dose. On day 2, PK assessment was repeated when subjects took saquinavir without ritonavir. Drug intake (with a standard meal containing 20 g of fat) was timed on days -1, 1 and 2. Geometric mean ratios (GMR) and 95% confidence intervals (CI) were calculated to assess changes in saquinavir PK parameters.
Geometric mean saquinavir AUC(0-12), C(trough), C(max) and elimination half-life on days 1 and 2 were 14 389 and 9590 ng.h/mL, 331 and 234 ng/mL, 2503 and 1893 ng/mL and 2.80 and 2.82 h, respectively. The GMR (95% CI) for these parameters were 0.67 (0.53-0.84), 0.71 (0.48-1.04), 0.76 (0.58-0.98) and 1.01 (0.86-1.18), respectively.
Withholding a ritonavir dose significantly reduces overall saquinavir exposure and C(max), but had no impact on the elimination half-life. These data establish the need to administer saquinavir and ritonavir simultaneously.
增强沙奎那韦硬胶囊（hg）血浆浓度所需的利托那韦剂量尚不清楚。减少利托那韦剂量可能有助于降低与利托那韦相关的副作用和成本。本研究考察了每日两次服用沙奎那韦-hg（1000毫克）并联合每日两次或单次每日一次服用100毫克利托那韦时的药代动力学情况。
18名每日两次服用沙奎那韦/利托那韦1000/100毫克的HIV感染成人，在早晨服用沙奎那韦/利托那韦剂量后的第1天接受沙奎那韦/利托那韦的药代动力学（PK）评估。在第2天，当受试者服用不含利托那韦的沙奎那韦时重复PK评估。在第-1、1和2天记录药物摄入时间（同时食用含20克脂肪的标准餐）。计算几何平均比值（GMR）和95%置信区间（CI）以评估沙奎那韦PK参数的变化。
第1天和第2天沙奎那韦的几何平均AUC(0 - 12)、C(谷值)、C(峰值)和消除半衰期分别为14389和9590纳克·时/毫升、331和234纳克/毫升、2503和1893纳克/毫升以及2.80和2.82小时。这些参数的GMR（95%CI）分别为0.67（0.53 - 0.84）、0.71（0.48 - 1.04）、0.76（0.58 - 0.98）和1.01（0.86 - 1.18）。
停用一剂利托那韦会显著降低沙奎那韦的总体暴露量和C(峰值)，但对消除半衰期无影响。这些数据表明需要同时给予沙奎那韦和利托那韦。
