Pokorná Pavla, Posch Lenka, Šíma Martin, Klement Petr, Slanar Ondrej, van den Anker John, Tibboel Dick, Allegaert Karel
a Department of Pediatrics, First Faculty of Medicine , Charles University in Prague and General University Hospital , Prague , Czech Republic.
b Institute of Pharmacology, First Faculty of Medicine , Charles University in Prague and General University Hospital in Prague , Prague , Czech Republic.
J Matern Fetal Neonatal Med. 2019 Jul;32(14):2302-2309. doi: 10.1080/14767058.2018.1432039. Epub 2018 Feb 5.
Phenobarbital (PB) pharmacokinetics (PK) in asphyxiated newborns show large variability, not only explained by hypothermia (HT). We evaluated potential relevant covariates of PK of PB in newborns treated with or without HT for hypoxic-ischemic encephalopathy (HIE).
Clearance (CL), distribution volume (Vd) and elimination half-life (t) were calculated using one-compartment analysis. Covariates were clinical characteristics (weight, gestational age, hepatic, renal, and circulatory status), comedication and HIE severity [time to reach normal aEEG pattern (TaEEG), dichotomous, within 24 h] and asphyxia severity [severe aspyhxia = pH ≤7.1 + Apgar score ≤5 (5 min), dichotomous]. Student's t-test, two-way ANOVA, correlation and Pearson's chi-square test were used.
Forty newborns were included [14 non-HT; 26 HT with TaEEG <24 h in 14/26 (group) and TaEEG ≥24 h in 12/26 (group)]. Severe asphyxia was present in 26/40 [5/14 non-HT, 11/14 and 10/12 in both HT groups]. PB-CL, Vd and t were similar between the non-HT and HT group. However, within the HT group, PB-CL was significantly different between group and group (p = .043). ANOVA showed that HT (p = .034) and severity of asphyxia (p = .038) reduced PB-CL (-50%).
The interaction of severity of asphyxia and HT is associated with a clinical relevant reduced PB-CL, suggesting the potential relevance of disease characteristics beyond HT itself.
窒息新生儿中苯巴比妥（PB）的药代动力学（PK）表现出很大的变异性，低温（HT）并非其唯一原因。我们评估了接受或未接受HT治疗的缺氧缺血性脑病（HIE）新生儿中PB PK的潜在相关协变量。
采用单室分析法计算清除率（CL）、分布容积（Vd）和消除半衰期（t）。协变量包括临床特征（体重、胎龄、肝脏、肾脏和循环状态）、合并用药以及HIE严重程度[达到正常aEEG模式的时间（TaEEG），二分法，24小时内]和窒息严重程度[重度窒息=pH≤7.1+阿氏评分≤5（5分钟），二分法]。使用学生t检验、双向方差分析、相关性分析和Pearson卡方检验。
纳入40例新生儿[14例未接受HT；26例接受HT，其中14/26例（组）TaEEG<24小时，12/26例（组）TaEEG≥24小时]。40例中有26例存在重度窒息[14例未接受HT的新生儿中有5例，接受HT的两组中分别有11/14例和10/12例]。未接受HT组和接受HT组之间的PB-CL、Vd和t相似。然而，在接受HT的组内，组与组之间的PB-CL存在显著差异（p=0.043）。方差分析显示，HT（p=0.034）和窒息严重程度（p=0.038）使PB-CL降低了50%。
窒息严重程度与HT的相互作用与临床相关的PB-CL降低有关，提示除HT本身外，疾病特征可能具有潜在相关性。
