Medizinische Klinik und Poliklinik II, Schwerpunkt Infektiologie, Universitätsklinikum Würzburg, ZIM Haus A3/A4, Oberdürrbacher Str. 6, 97080, Würzburg, Germany.
Department of Pediatrics and Child Health, Ward A9, Tygerberg Hospital, University of Stellenbosch, Francie van Zijl Drive, Tygerberg, 7505, South Africa.
Med Microbiol Immunol. 2018 Nov;207(5-6):339-343. doi: 10.1007/s00430-018-0550-5. Epub 2018 Jul 4.
The role of therapeutic drug monitoring in pediatric antiretroviral therapy is unclear. A little pharmacokinetic datum from clinical practice exists beyond controlled approval studies including clinically stable children. The aim of this study is to quantify LPV exposure of critically ill infants in an ICU and-by identifying risk factors for inadequate exposure-to define sensible indications for TDM in pediatric HIV care; in addition, assume total drug adherence in ICU to compare LPV exposure with a setting of unknown adherence. In this prospective investigation, 15 blood samples from critically ill infants in the pediatric ICU at Tygerberg Hospital were analyzed for LPV-serum concentrations. They were then compared to those of 22 blood samples from out-patient children. Serum-level measurements were performed with an established high-performance liquid chromatography method. All LPV-serum levels of ICU patients were higher than a recommended C (= 1.000 ng/ml), 60% of levels were higher than C (8.200 ng/ml). Partly, serum levels reached were extremely high (Maximum: 28.778 ng/ml). Low bodyweight and age correlated significantly with high LPV concentrations and were risk factors for serum levels higher than C. Significantly fewer serum levels from infants in ICU care (mean: 11.552 ng/ml ± SD 7760 ng/ml) than from out-patient children (mean: 6.756 ng/ml ± SD 6.003 ng/ml) were subtherapeutic (0 vs. 28%, p = 0.008). Under total adherence in the ICU group, there were no subtherapeutic serum levels, while, in out-patient, children with unknown adherence 28% of serum levels were found subtherapeutic. Low bodyweight and age are risk factors for reaching potentially toxic LPV levels in this extremely fragile population. TDM can be a reasonable tool to secure sufficient and safe drug exposure in pediatric cART.
在儿科抗逆转录病毒治疗中，治疗药物监测的作用尚不清楚。除了经过对照批准的研究外，在临床稳定的儿童中还存在少量药代动力学数据。本研究的目的是定量检测 ICU 中危重症婴儿的 LPV 暴露情况，并通过确定暴露不足的风险因素，为儿科 HIV 护理中的 TDM 提供合理的依据；此外，在 ICU 中假设患者的药物总依从性，以比较 LPV 暴露与未知依从性设置的情况。在这项前瞻性研究中，对 Tygerberg 医院儿科 ICU 中 15 名危重症婴儿的 15 份血样进行了 LPV-血清浓度分析。然后将这些结果与 22 名门诊患儿的血样进行了比较。采用建立的高效液相色谱法进行血清水平检测。所有 ICU 患者的 LPV 血清水平均高于推荐的 C（=1.000ng/ml），60%的水平高于 C（8.200ng/ml）。部分患者的血清水平极高（最高：28.778ng/ml）。低体重和年龄与 LPV 浓度显著相关，是血清水平高于 C 的危险因素。与门诊儿童相比，来自 ICU 患儿的血清水平（中位数：11.552ng/ml±SD7760ng/ml）中明显较少达到治疗范围（中位数：6.756ng/ml±SD6.003ng/ml）（0%比 28%，p=0.008）。在 ICU 组中，在完全依从的情况下，没有治疗范围以下的血清水平，而在门诊儿童中，未知依从的患儿有 28%的血清水平未达到治疗范围。低体重和年龄是该极其脆弱人群中达到潜在毒性 LPV 水平的危险因素。TDM 可以成为确保儿科 cART 中药物充分和安全暴露的合理工具。
