Jackson Akil, Moyle Graeme, Dickinson Laura, Back David, Khoo Saye, Taylor Jessica, Gedela Keerti, Abongomera George, Gazzard Brian, Boffito Marta
St Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
Antivir Ther. 2012;17(1):19-24. doi: 10.3851/IMP1910.
Here, we aimed to investigate the pharmacokinetics of abacavir and carbovir triphosphate (CBV-TP) with darunavir/ritonavir 900/100 mg once daily or raltegravir 400 mg twice daily.
HIV-infected subjects on abacavir (600 mg once daily) underwent steady-state pharmacokinetic assessments without and with darunavir/ritonavir or raltegravir. Within-subject changes in plasma and intracellular pharmacokinetic parameters were evaluated by geometric mean ratios (GMRs) and 90% CIs.
A total of 19 patients completed the study. With darunavir/ritonavir (versus abacavir alone), abacavir GMRs (90% CI) were 0.73 (0.66, 0.80), 0.62 (0.50, 0.77) and 0.78 (0.69, 0.87) for area under the curve (AUC), trough concentration (C(trough)) and maximum concentration (C(max)), respectively. With raltegravir, they were 1.03 (0.97, 1.10), 0.83 (0.62, 1.11) and 1.06 (0.95, 1.18), respectively. Intracellular CBV-TP GMRs (90% CI) were 0.88 (0.72, 1.07), 0.68 (0.48, 0.95) and 0.98 (0.79, 1.23) for AUC, C(trough) and C(max), respectively, with darunavir/ritonavir, and 0.96 (0.76, 1.20), 0.57 (0.33, 1.00) and 1.07 (0.85, 1.35), respectively, with raltegravir.
There was a 27% decrease in abacavir plasma exposure with darunavir/ritonavir and no changes with raltegravir. CBV-TP C(trough) was significantly decreased with darunavir/ritonavir (32%) and showed a high inter-individual variability with raltegravir.
在此，我们旨在研究阿巴卡韦和三磷酸卡波韦（CBV-TP）与每日一次服用900/100毫克的达芦那韦/利托那韦或每日两次服用400毫克的雷特格韦合用时的药代动力学。
接受阿巴卡韦（每日一次600毫克）治疗的HIV感染受试者在未服用和服用达芦那韦/利托那韦或雷特格韦的情况下进行了稳态药代动力学评估。通过几何平均比值（GMRs）和90%置信区间评估血浆和细胞内药代动力学参数的个体内变化。
共有19名患者完成了该研究。与达芦那韦/利托那韦合用（与单独使用阿巴卡韦相比）时，阿巴卡韦的曲线下面积（AUC）、谷浓度（C(trough)）和最大浓度（C(max)）的GMRs（90%置信区间）分别为0.73（0.66，0.80）、0.62（0.50，0.77）和0.78（0.69，0.87）。与雷特格韦合用时，它们分别为1.03（0.97，1.10）、0.83（0.62，1.11）和1.06（0.95，1.18）。与达芦那韦/利托那韦合用时，细胞内CBV-TP的AUC、C(trough)和C(max)的GMRs（90%置信区间）分别为0.88（0.72，1.07）、0.68（0.48，0.95）和0.98（0.79，1.23），与雷特格韦合用时分别为0.96（0.76，1.20）、0.57（0.33，1.00）和1.07（0.85，1.35）。
与达芦那韦/利托那韦合用时，阿巴卡韦的血浆暴露量降低了27%，与雷特格韦合用时无变化。与达芦那韦/利托那韦合用时，CBV-TP的C(trough)显著降低（32%），与雷特格韦合用时个体间变异性较高。
