Moltó José, Blanco Asunción, Miranda Cristina, Miranda José, Puig Jordi, Valle Marta, Delavarga Meritxell, Fumaz Carmina R, Barbanoj Manuel José, Clotet Bonaventura
'Lluita contra la SIDA' Foundation, Germans Trias i Pujol Hospital, Badalona, Barcelona, Spain.
Br J Clin Pharmacol. 2007 Jun;63(6):715-21. doi: 10.1111/j.1365-2125.2006.02834.x. Epub 2007 Jan 12.
The objective of this study was to assess interindividual variability in plasma trough concentrations of non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) among HIV-infected adults in an outpatient routine clinical practice setting.
The study included 117 patients who attended our clinic for routine outpatient blood tests and who were receiving antiretroviral therapy which included NNRTI or PI. Patients were not informed that drug concentrations were going to be assessed until blood sampling. The time of the last antiretroviral treatment intake and blood sampling were recorded. Drug concentrations were considered optimal if they were above the proposed minimum effective concentration. In addition, efavirenz, nevirapine and atazanavir concentrations were considered potentially toxic if they were higher than 4.0 mg l(-1), 6.0 mg l(-1), and 0.85 mg l(-1), respectively.
Overall, interindividual variability in NNRTI and PI plasma concentrations was approximately 50%, and only 68.4% of the patients had drug concentrations within the proposed therapeutic range. Inappropriate adherence only explained 35% of subtherapeutic drug concentrations.
Interindividual variability in trough concentrations of NNRTI and PI among HIV-infected adults is large in routine clinical practice, with drug concentrations being outside the therapeutic window in a significant proportion of patients. Therapeutic drug monitoring may be useful to guide antiretroviral therapy in clinical practice.
本研究的目的是评估在门诊常规临床实践环境中,感染人类免疫缺陷病毒(HIV)的成年人中非核苷类逆转录酶抑制剂(NNRTI)和蛋白酶抑制剂(PI)的血浆谷浓度的个体间变异性。
该研究纳入了117名到我们诊所进行常规门诊血液检查且正在接受包含NNRTI或PI的抗逆转录病毒治疗的患者。在采血前,患者未被告知要评估药物浓度。记录最后一次抗逆转录病毒治疗服药时间和采血时间。如果药物浓度高于建议的最低有效浓度,则认为是最佳的。此外,如果依非韦伦、奈韦拉平和阿扎那韦的浓度分别高于4.0 mg l⁻¹、6.0 mg l⁻¹和0.85 mg l⁻¹,则认为具有潜在毒性。
总体而言,NNRTI和PI血浆浓度的个体间变异性约为50%,只有68.4%的患者药物浓度在建议的治疗范围内。服药依从性不佳仅解释了35%的治疗不足的药物浓度情况。
在常规临床实践中,感染HIV的成年人中NNRTI和PI谷浓度的个体间变异性很大,相当一部分患者的药物浓度超出治疗窗。治疗药物监测可能有助于指导临床实践中的抗逆转录病毒治疗。