Institute of Clinical Infectious Diseases, Catholic University of Sacred Heart, Rome, Italy.
Pharmacol Res. 2011 Mar;63(3):249-53. doi: 10.1016/j.phrs.2010.11.009. Epub 2010 Dec 2.
The present study aimed to investigate potential drug interactions between darunavir and raltegravir in patients treated for HIV infection. We enrolled HIV-infected subjects on darunavir-containing regimens that underwent measurement of plasma darunavir trough concentration (12±3 h after dosing). Two groups of patients were compared: those taking darunavir plus a nucleoside/nucleotide backbone (group 1) or a backbone+raltegravir (group 2). Interindividual pharmacokinetic variability was evaluated through the coefficient of variation (CV(inter)). We obtained 156 plasma samples from 63 patients, of which 44 in group 1 and 19 in group 2. Overall, darunavir geometric mean concentration was 2.90 mg/L (95% CI 2.34-3.60) while ritonavir geometric mean concentration was 0.21 mg/L (95% CI 0.17-0.27). We observed a high inter-individual variability in darunavir (CV(inter) 59%) and ritonavir (CV(inter) 103%) plasma levels. Darunavir concentration correlated with concomitant ritonavir levels (r=0.476, p<0.001). Patients in group 1 had a higher darunavir geometric mean concentration than those in group 2 [3.44 mg/L (95% CI 2.79-4.23) versus 1.95 mg/L (95% CI 1.19-3.20), p=0.017]. However, the proportion of subjects with concomitant HIV-RNA <50 copies/mL was higher in group 2 (78.9% versus 47.7%, p=0.028). In a multivariable model, raltegravir co-administration was independently related to a lower darunavir concentration (mean difference -0.25 log(10) mg/L, 95% CI -0.46/-0.04, p=0.020) after adjusting for time from last drug intake and concomitant drugs used. In conclusion, a potential drug interaction between darunavir and raltegravir was observed, although this did not seem virologically significant. For the distinct metabolic pathways of these drugs, its mechanism remains to be determined.
本研究旨在探讨达芦那韦和拉替拉韦联合治疗 HIV 感染患者的潜在药物相互作用。我们招募了正在接受达芦那韦为基础的治疗方案且接受了达芦那韦谷浓度（服药后 12±3 小时）检测的 HIV 感染患者。我们比较了两组患者：一组服用达芦那韦加核苷/核苷酸类似物（组 1），另一组服用达芦那韦加拉替拉韦（组 2）。通过变异系数（CV(inter)）评估个体间的药代动力学变异性。我们从 63 名患者中获得了 156 份血浆样本，其中 44 份来自组 1，19 份来自组 2。总体而言，达芦那韦几何平均浓度为 2.90mg/L（95%CI 2.34-3.60），利托那韦几何平均浓度为 0.21mg/L（95%CI 0.17-0.27）。我们观察到达芦那韦（CV(inter) 59%）和利托那韦（CV(inter) 103%）血浆水平存在高度的个体间变异性。达芦那韦浓度与同时存在的利托那韦水平相关（r=0.476，p<0.001）。组 1 患者的达芦那韦几何平均浓度高于组 2 [3.44mg/L（95%CI 2.79-4.23）比 1.95mg/L（95%CI 1.19-3.20），p=0.017]。然而，组 2 中同时 HIV-RNA<50 拷贝/mL 的患者比例更高（78.9%比 47.7%，p=0.028）。在多变量模型中，调整最后一次服药时间和同时使用的药物后，拉替拉韦联合用药与达芦那韦浓度降低独立相关（平均差值-0.25log(10)mg/L，95%CI-0.46/-0.04，p=0.020）。结论：尽管未观察到病毒学意义，但达芦那韦和拉替拉韦之间存在潜在的药物相互作用。由于这些药物的代谢途径不同，其机制仍需确定。
