Increased Aripiprazole Concentrations in an HIV-Positive Male Concurrently Taking Duloxetine, Darunavir, and Ritonavir
Increased Aripiprazole Concentrations in an HIV-Positive Male Concurrently Taking Duloxetine, Darunavir, and Ritonavir
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DOI：
10.1345/aph.1p139
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发表时间：
2010-11-01
影响因子：
2.9
通讯作者：
Kawamoto, Laura S.
中科院分区：
文献类型：
--
作者：
Aung, Gregory L.;O'Brien, John G.;Kawamoto, Laura S.
目的：报道一例阿立哌唑与达鲁那韦、利托那韦和度洛西汀联合用药期间血药浓度升高的病例。CASE摘要：一名43岁的HIV阳性拉美裔男子在阿立哌唑和度洛西汀的基础上接受达鲁那韦/利托那韦抗逆转录病毒疗法(ART)治疗抑郁和焦虑。在阿立哌唑剂量增加到每天50毫克一个月后，患者出现了混乱和协调能力丧失。几周后，他出现发烧、咳嗽、头痛、颈部僵硬、背部疼痛和视力模糊的情况，并因可能的脑膜炎入院。由于住院期间疼痛控制和静脉输液改善了症状，他在入院后几天内就出院了。一个月后，他因症状恶化再次入院，由此产生的诊断检查显示，除了淋巴结病(LAD)外，其他结果并不显著。这一发现被归因于他第一次入院后停止了艺术。他每天服用阿立哌唑50 mg，达鲁那韦800 mg，利托那韦100 mg，度洛西汀60 mg。阿立哌唑的随机稳态浓度为1100 ng/m L(治疗浓度为100-200 ng/m L)。讨论：Horn药物相互作用概率量表显示阿立哌唑浓度升高可能与达鲁那韦、利托那韦和度洛西汀合用有关，达鲁那韦/利托那韦和度洛西汀对细胞色素P3A4和2D6有抑制作用。浓度升高的潜在混杂因素包括度洛西汀抑制CYP2D6多态，可能的2D6多态，以及超过阿立哌唑的最大剂量。最初出现的混乱和协调障碍可能是阿立哌唑中毒的早期迹象，入院前的症状表明阿立哌唑复发。结论：阿立哌唑与达鲁那韦、利托那韦和度洛西汀之间的相互作用可能是显著的。临床医生应该意识到，在同时服用利托那韦增强的抗逆转录病毒药物和其他细胞色素P450抑制剂(如度洛西汀)的同时，艾滋病毒阳性患者发生阿立哌唑中毒的风险增加。剂量调整或监测参数应该是一个研究和讨论的领域。
OBJECTIVE: To report a case of increased aripiprazole concentrations during coadministration with darunavir, ritonavir, and duloxetine.CASE SUMMARY: A 43-year-old HIV-positive Hispanic man received darunavir/ ritonavir-based antiretroviral therapy (ART) in addition to aripiprazole and duloxetine for depression and anxiety. A month after the aripiprazole dosage was increased to 50 mg daily, the patient developed confusion and loss of coordination. Weeks later, he presented to the emergency department with fever, cough, headache, neck stiffness, back pain, and blurred vision and was admitted for possible meningitis. Because symptoms improved with pain control and intravenous fluids during hospitalization, he was discharged within a couple days after admission. One month later he was readmitted for worsening symptoms, and the resulting diagnostic workup showed unremarkable findings except for lymphadenopathy (LAD). This finding was attributed to discontinuing ARTs after his first admission. He was discharged on aripiprazole 50 mg daily, darunavir 800 mg daily, ritonavir 100 mg daily, and duloxetine 60 mg daily. A random steady-state concentration of aripiprazole was 1100 ng/mL (therapeutic concentration 100-200 ng/mL) obtained 49 days after discharge.DISCUSSION: The Horn Drug Interaction Probability Scale demonstrated a possible relationship between the increased aripiprazole concentration and coadministration of darunavir/ritonavir and duloxetine, which inhibit CYP3A4 and 2D6. Potential confounders to the increased concentration include duloxetine inhibition of CYP2D6 polymorphism, possible 2D6 polymorphism, and exceeding aripiprazole's maximum dose. The initial presentation of confusion and loss of coordination may have been early signs of aripiprazole toxicity, which relapsed as shown by his symptoms prior to admission.CONCLUSIONS: The interaction between aripiprazole and darunavir, ritonavir, and duloxetine may be significant. Clinicians should be cognizant of increased risk of aripiprazole toxicity in HIV-positive patients concurrently taking ritonavir-boosted ART and other cytochrome P450 inhibitors like duloxetine. Dose adjustments or monitoring parameters should be an area of research and discussion.