Autar R S, Ananworanich J, Apateerapong W, Sankote J, Hill A, Hirschel B, Cooper D, Lange J, Phanuphak P, Ruxrungtham K, Burger D
The HIV Netherlands Australia Thailand Research Collaboration, The Thai Red Cross AIDS Research Center, Bangkok, Thailand.
J Antimicrob Chemother. 2004 Oct;54(4):785-90. doi: 10.1093/jac/dkh415. Epub 2004 Aug 25.
A pharmacokinetic comparison of three dosing regimens of saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily.
Twenty patients on saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) and elimination half-life were calculated using a non-compartmental model.
Compared with saquinavir/ritonavir 1600/100 mg once-daily dosing, the saquinavir AUC and Cmin improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low Cmin in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in saquinavir Cmax (52%) compared with saquinavir/ritonavir 1600/100 mg once-daily.
Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher saquinavir plasma levels compared with saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferred.
对三种沙奎那韦/利托那韦给药方案进行药代动力学比较：每日一次1600/100毫克与每日两次1000/100毫克，以及每日一次1600/100毫克与每日一次2000/100毫克。
招募20名服用沙奎那韦硬胶囊/利托那韦每日一次1600/100毫克并联合两种核苷类逆转录酶抑制剂至少4周的患者，将其随机分为每日两次服用沙奎那韦硬胶囊/利托那韦1000/100毫克组或每日一次服用2000/100毫克组。在基线（第0天）和换药后7天绘制两条药代动力学曲线。通过经验证的高效液相色谱法（HPLC）在服药后0、2、4、6、8、10、12小时（每日一次给药为24小时）测定血浆浓度。使用非房室模型计算血浆浓度-时间曲线下面积（AUC0-24或AUC0-12）、最大和最小浓度（Cmax和Cmin）以及消除半衰期。
与每日一次服用沙奎那韦/利托那韦1600/100毫克相比，每日两次服用1000/100毫克（分别提高53%和299%）以及每日一次服用2000/100毫克（分别提高71%和65%）时，沙奎那韦的AUC和Cmin显著改善。三名基线时Cmin较低的受试者在换用其他剂量后得到纠正。与每日一次服用沙奎那韦/利托那韦1600/100毫克相比，每日一次服用沙奎那韦/利托那韦2000/100毫克还使沙奎那韦的Cmax显著增加（52%）。
与每日一次服用沙奎那韦/利托那韦1600/100毫克相比，每日一次服用2000/100毫克或每日两次服用1000/100毫克的沙奎那韦/利托那韦可使沙奎那韦血浆水平更高。考虑到每日一次给药的便利性，每日一次服用2000/100毫克的剂量可能更佳。
