Toxicokinetics of paraquat in Korean patients with acute poisoning

Abstract

To conduct a kinetic study of paraquat (PQ), we investigated 9 patients with acute PQ intoxication. All of them ingested more than 20 ml of undiluted PQ herbicide to commit suicide and arrived at our hospital early, not later than 7 h after PQ ingestion. The urine dithionite test for PQ in all of the nine patients was strongly positive at emergency room. Blood samples were obtained every 30 min for the first 2~3 h and then every 1 or 2 h, as long as the clinical progression was stable among the patients for 30 h after PQ ingestion. The area under the plasma concentration-time curve (AUCinf), which was extrapolated to infinity, was calculated using the trapezoidal rule. Toxicokinetic parameters, such as the terminal elimination half-life, apparent oral clearance, and apparent volume of distribution (Vd/F) were calculated. The maximum PQ concentration (Cmax) and the time to reach maximum PQ concentration (Tmax) were also obtained. Plasma PQ concentrations in nine patients were well described by a bi-exponential curve with a mean terminal elimination half-life of 13.1±6.8 h. Cmax and AUCinf were 20.8±25.7 mg/l and 172.5±160.3 h·mg/l, respectively. Apparent volume of distribution and apparent oral clearance were 50.9±61.3 l/kg and 173.4±111.2 l/h, respectively. There were a significant correlation (r =0.84; p<0.05) between the PQ amount ingested and Cmax. AUCinf also showed a significant correlation (r =0.83; p<0.05) with the PQ amount ingested. These correlations provide evidence that PQ has dose-linear toxicokinetic characteristics.

Alveolar–arterial partial pressure difference as an early predictor for patients with acute paraquat poisoning

“… 12 All patients were admitted to the hospital in accordance with standard medical emergency procedures. 13 …”

“… 12 Therefore, an effective treatment was described as patients who survived more than 3 months after PQ poisoning, had stable vital signs, and had no evidence of progressive organ failure (especially the kidneys and lungs). 13 We also determined survival using medical records or telephone follow-up.…”

“…12 All patients were admitted to the hospital in accordance with standard medical emergency procedures. 13 We recorded information, such as age, sex, symptoms, the amount of PQ ingested, a dithionite urine test for PQ, the time of the first gastric lavage, and the treatment outcome. Arterial blood gas analysis was required to be performed in the morning on days 1, 3, 7, 14, and 21.…”

Plasma Concentration After the First Hemoperfusion has a High Predictive Value in Medium Level Acute Paraquat-Poisoned Patients

“…18 Some scholars believe that PQ is quickly absorbed, retained in plasma for a short period, and is rapidly distributed to all body parts, with its toxic metabolism presenting characteristics of a 2-compartment model. 19 In addition, in the early stage of poisoning, the kidneys have a robust endogenous clearance capacity for PQ. Therefore, the additional clearance of HP cannot achieve the desired clinical effect.…”

Effects of curcumin on artery blood gas index of rats with pulmonary fibrosis caused by paraquat poisoning and the expression of Smad 4, Smurf 2, interleukin‑4 and interferon‑γ

“…However, paraquat is also one of the herbicides mostly used for suicide. Paraquat has caused 20 deaths per million people worldwide, and the mortality rate is 60–70% (2,3). Paraquat poisoning toxicity involves multiple organs such as the digestive tract, skin and respiratory tract, which can lead to multiple organ dysfunction syndrome and renal failure (4).…”