Brodifacoum pharmacokinetics in acute human poisoning: implications for estimating duration of vitamin K therapy.
Brodifacoum pharmacokinetics in acute human poisoning: implications for estimating duration of vitamin K therapy.
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DOI：
10.1080/24734306.2021.1887637
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发表时间：
2021
影响因子：
--
通讯作者：
Feinstein DL
中科院分区：
文献类型：
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作者：
Nosal DG;van Breemen RB;Haffner JW;Rubinstein I;Feinstein DL
长效抗凝灭鼠剂 (LAAR) 中毒患者的护理标准后续治疗是每日高剂量（每天高达 100 毫克）口服维生素 K1 (VK1)，持续数周至数月至一年多。 CLIA 认证的血浆 LAAR 浓度定量检测现在可以帮助医疗保健提供者确定何时安全地停止 VK1 治疗。我们使用从吸入含有 BDF 的合成大麻素后中毒的患者获得的血浆 Brodifacoum （BDF，一种强效 LAAR）浓度的连续测量，提出了达到安全浓度（< = 10ng/ml）所需的治疗持续时间的估计。我们将数据拟合到零阶（线性）和一阶（指数）曲线，后者用于解释 BDF 的肠肝循环。结果表明，当假设清除率呈指数时，治疗持续时间的估计值显着更长。因此，我们建议在中毒患者随访期间同时监测血浆 BDF 浓度和国际标准化比值 (INR)，并在 VK1 治疗停止后测定浓度，以记录安全浓度的持续情况。
Standard of care follow-up therapy for patients poisoned by long-acting anticoagulant rodenticides (LAARs) is daily high-dose (up to 100 mg per day) oral vitamin K1 (VK1) for weeks to months to over a year. The availability of CLIA-certified quantitative testing for plasma LAAR concentrations can now assist health care providers in determining when to safely discontinue VK1 therapy. We present estimates of treatment duration required to reach safe concentrations (< =10ng/ml) using serial measurements of plasma brodifacoum (BDF, a potent LAAR) concentrations obtained from patients poisoned after inhaling synthetic cannabinoids containing BDF. We fit the data to zero-order (linear) and first-order (exponential) curves, the latter to account for enterohepatic circulation of BDF. The results show that estimates of therapy duration are significantly longer when exponential clearance is assumed. Accordingly, we recommend that plasma BDF concentrations be monitored simultaneously with international normalization ratio (INR) during follow-up of poisoned patients, and that concentrations be determined after VK1 therapy is discontinued to document persistence of safe concentrations.