Observational studyTherapeutic drug monitoring2026
Paracetamol Half-Life Declines over Time After an Acute Overdose.
Observational study in Therapeutic drug monitoring, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
backgroundParacetamol poisoning is one of the most common types of drug-induced poisoning worldwide and can cause severe hepatotoxicity. Acetylcysteine administration is the most effective intervention to prevent hepatotoxicity. Clinically, we observed multiple cases in which the initially prolonged paracetamol half-life decreased during acetylcysteine treatment. This study aimed to investigate the changes in the half-life of paracetamol in patients with paracetamol poisoning treated with acetylcysteine.
methodsThis was a retrospective observational study on patients with paracetamol poisoning who were treated with acetylcysteine. Patients with ≥3 paracetamol plasma concentrations during a single acute overdose were selected from 2 hospitals in the Netherlands. The half-lives of paracetamol in these patients were calculated using consecutive samples. A moderately prolonged paracetamol half-life was defined as a first half-life of >4.0 hours and a severely prolonged paracetamol half-life of >5.5 hours.
resultsSeventy-one paracetamol overdoses from 59 patients were included. The half-life of paracetamol changed from 4.6 (3.5-8.2) h for the first half-life to 2.9 (2.1-3.8) hours for the second half-life ( P < 0.001). In 20 cases (28%), the initial half-life was moderately prolonged (4.0-5.5 hours), and in 26 cases (37%), it was severely prolonged (>5.5 hours). In all 3 subgroups, the half-life decreased significantly between the first and second half-lives ( P < 0.001). The reported ingested dose, 4-hour paracetamol concentration, and time to acetylcysteine administration did not differ between the subgroups.
conclusionsOur results suggest that the half-life of paracetamol decreases during acetylcysteine treatment. Health care professionals should consider repeated measurements of paracetamol concentrations and calculation of half-lives when using paracetamol half-life as a marker of hepatotoxicity, particularly when deciding whether to extend acetylcysteine treatment beyond the duration stated in the current guidelines.
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