Brodifacoum pharmacokinetics in acute human poisoning: implications for estimating duration of vitamin K therapy

Abstract

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.

Keywords: Brodifacoum; rodenticide; synthetic cannabinoids; vitamin K1.

Figure 1.

Correlation of calculated VK1 therapy times to plasma BDF concentrations. The ratio of zero-order to first-order calculated times required to reach 10 ng/ml are plotted versus the plasma BDF level measured in the first available sample for each case. P = 0.020, Pearson correlation analysis.