Northern Alberta HIV Program and Regional Pharmacy Services, Alberta Health Services, Edmonton, AB, Canada.
Ann Pharmacother. 2009 Dec;43(12):2117-20. doi: 10.1345/aph.1M393. Epub 2009 Nov 24.
To report the results of therapeutic drug monitoring of lopinavir/ritonavir and itraconazole concentrations in an HIV-infected male who was treated for histoplasmosis.
A 34-year-old HIV-infected man who had recently initiated efavirenz-based antiretroviral therapy was diagnosed with disseminated Histoplasma capsulatum infection. In the hospital, lopinavir/ritonavir 400 mg/100 mg twice daily replaced efavirenz to avoid efavirenz-itraconazole interactions. After 14 days of liposomal amphotericin B therapy, itraconazole solution was initiated at 150 mg twice daily for 3 days, followed by 200 mg daily. Prior to itraconazole initiation, lopinavir trough concentration was 7.4 mg/L. The lopinavir trough concentration 15 days later, after 14 days of itraconazole, was 6.8 mg/L. An itraconazole concentration measured 2 hours post-dose on day 15 of oral therapy was 1.9 microg/mL. After 2 weeks of liposomal amphotericin, urine Histoplasma antigen was 27.23 ng/mL; after 5 months of oral itraconazole therapy, it decreased to 5.24 ng/mL. Plasma HIV RNA decreased 4.26 log(10) in 5 months to less than 40 copies/mL. The patient has demonstrated marked clinical improvement.
In this case, dosing recommendations of itraconazole 200 mg daily with lopinavir/ritonavir were appropriate. Lopinavir trough concentrations were not significantly different following the addition of itraconazole and were above the minimum target of 1 mg/L in treatment-naïve patients. The itraconazole concentration was above the recommended concentration of at least 1 microg/mL.
The dose of itraconazole was reduced to 200 mg daily as recommended by current guidelines, and therapeutic drug monitoring of both itraconazole and lopinavir concentrations confirmed that no further dosage adjustments were necessary.
报告 1 例 HIV 感染者在治疗组织胞浆菌病时洛匹那韦/利托那韦和伊曲康唑浓度的治疗药物监测结果。
一名 34 岁的 HIV 感染者，最近开始接受依非韦伦为基础的抗逆转录病毒治疗，被诊断为播散性荚膜组织胞浆菌感染。在医院中，洛匹那韦/利托那韦 400mg/100mg，每日两次，替代依非韦伦，以避免依非韦伦-伊曲康唑相互作用。在 14 天的两性霉素 B 脂质体治疗后，开始每日两次给予伊曲康唑溶液 150mg，持续 3 天，然后每日 200mg。在开始伊曲康唑之前，洛匹那韦谷浓度为 7.4mg/L。在伊曲康唑治疗 14 天后的第 15 天，洛匹那韦谷浓度为 6.8mg/L。在口服治疗第 15 天，伊曲康唑给药后 2 小时的伊曲康唑浓度为 1.9μg/ml。经过 2 周的两性霉素 B 脂质体治疗，尿荚膜组织胞浆菌抗原为 27.23ng/ml；经过 5 个月的伊曲康唑口服治疗，抗原降至 5.24ng/ml。血浆 HIV RNA 在 5 个月内下降 4.26log10，降至小于 40 拷贝/ml。患者表现出明显的临床改善。
在这种情况下，伊曲康唑每日 200mg 与洛匹那韦/利托那韦联合用药的推荐剂量是合适的。在添加伊曲康唑后，洛匹那韦的谷浓度没有显著差异，且高于治疗初治患者的最小目标值 1mg/L。伊曲康唑浓度高于推荐的至少 1μg/ml 的浓度。
根据当前指南，将伊曲康唑的剂量减少至每日 200mg，伊曲康唑和洛匹那韦浓度的治疗药物监测证实，无需进一步调整剂量。
