Abstract:
Objective To investigate the clearance effects of hemoperfusion (HP), intralipid fat emulsion (IFE), and their combination on fenthion in rabbit blood, as well as their influences on toxicokinetic and toxicodynamic indicators of fenthion administration, and to preliminarily explore the efficacy of combined application in enhancing fenthion clearance.
Methods Twenty male rabbits (90 to 120 days old) were intravenously administered fenthion (10 mg/kg) and then randomly divided into four groups (n = 5) according to the random number table method: control group (no intervention), IFE group (slow infusion of 10 mL IFE over 1 h), HP group (immediate HP for 2 h), and combined HP+IFE group (immediate HP for 2 h together with 10 mL IFE infusion over 1 h). Arterial blood samples (1 mL) were collected at various time points to measure plasma fenthion concentrations, toxicokinetic indicators, and toxicodynamic indicators.
Results Compared with the control group, the IFE group, HP group, and combined HP+IFE group showed significant decreases in the toxicokinetic parameters, including the area under the curve AUC(0 ~ t)、AUC(0 ~ ∞), the area under the first moment curve AUMC(0 ~ t)、AUMC(0 ~ ∞), the mean residence time MRT(0 ~ t)、MRT(0 ~ ∞), the variance of residence time VRT(0 ~ t)、VRT(0 ~ ∞), the concentration at the last time point (Clast), and the half-life calculated by statistical moments (t1/2z) (all P < 0.05). However, pairwise comparisons among the IFE group, HP group, and combined HP+IFE group showed no statistically significant differences in any of the toxicokinetic parameters (all P > 0.05). Toxicodynamic results indicated no statistically significant interaction among the different treatment groups (all P > 0.05); for each indicator, there was no interaction effect between group and time.
Conclusions HP, IFE, and their combination can all reduce fenthion concentrations and the toxic load in rabbits. Although a synergistic advantage of combining HP with IFE for clearing fenthion from rabbit blood has not yet been demonstrated, this study preliminarily validates the safety and feasibility of the combined regimen, providing a basis for optimizing the timing, dosage, and duration of IFE treatment in future studies.