Tissue time course and bioavailability of the pyrethroid insecticide bifenthrin in the Long-Evans rat

Abstract

1. Pyrethroids are neurotoxic and parent pyrethroid appears to be toxic entity. This study evaluated the oral disposition and bioavailability of bifenthrin in the adult male Long-Evans rat. 2. In the disposition study, rats were administered bifenthrin (0.3 or 3 mg/kg) by oral gavage and serially sacrificed (0.25 h to 21 days). Blood, liver, brain and adipose tissue were removed. In the bioavailability study, blood was collected serially from jugular vein cannulated rats (0.25 to 24 h) following oral (0.3 or 3 mg/kg) or intravenous (0.3 mg/kg) administration of bifenthrin. Tissues were extracted and analyzed for bifenthrin by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). 3. Bifenthrin concentration in blood and liver peaked 1-2-h postoral administration and were approximately 90 ng/ml (or g) and 1000 ng/ml (or g) for both tissues at 0.3 and 3 mg/kg, respectively. Bifenthrin was rapidly cleared from both blood and liver. Brain concentrations peaked at 4-6 h and were lower than in blood at both doses (12 and 143 ng/g). Bifenthrin in adipose tissue peaked at the collected time points of 8 (157 ng/g) and 24 (1145 ng/g) h for the 0.3 and 3 mg/kg doses, respectively and was retained 21 days postoral administration. Following intravenous administration, the blood bifenthrin concentration decreased bi-exponentially, with a distribution half-life of 0.2 h and an elimination half-life of 8 h. Bifenthrin bioavailability was approximately 30%. These disposition and kinetic bifenthrin data may decrease uncertainties in the risk assessment for this pyrethroid insecticide.

Successful treatment of bifenthrin toxicosis using therapeutic plasma exchange

“…Bifenthrin's pharmacokinetic profile has not been described in dogs; however, in rodent models, bifenthrin appears to be rapidly absorbed both by oral and inhalational routes, and the compound has a large volume of distribution. 11,12 It is important to note that because the patient in the current report was exposed to a powdered bifenthrin product, it is possible that the route of inhalation may have played a role in the severity of exposure. When rodents were given multiple doses of bifenthrin per os, no observable adverse effects were noted.…”

“…The elimination half-life was reported to be 3 hours and would be expected to be more reflective of distribution as opposed to IV administration, in which the brain elimination half-life was up to 13 hours. 11,12 In general, pyrethroid compounds have reportedly high plasma protein binding. 13 The standard use of TPE is for compounds with a low volume of distribution, long half-lives, and high plasma protein binding.…”

“…Because this dog was exposed to a toxic dose of bifenthrin, it is plausible that the drug clearance would have been decreased and elimination half-life longer due to saturation of the hepatic enzyme system. 8,11,12 The recent use of intralipids may have resulted in the capture of more protein-bound drug in the intravascular compartment by TPE. Given the paucity of information regarding bifenthrin toxicosis in dogs and the patient's minimal response to standard medical management after 12 hours, TPE was instituted in this case.…”

“…When rodents were given multiple doses of bifenthrin per os, no observable adverse effects were noted. The elimination half‐life was reported to be 3 hours and would be expected to be more reflective of distribution as opposed to IV administration, in which the brain elimination half‐life was up to 13 hours 11,12 . In general, pyrethroid compounds have reportedly high plasma protein binding 13 .…”

“…The standard use of TPE is for compounds with a low volume of distribution, long half‐lives, and high plasma protein binding. Because this dog was exposed to a toxic dose of bifenthrin, it is plausible that the drug clearance would have been decreased and elimination half‐life longer due to saturation of the hepatic enzyme system 8,11,12 . The recent use of intralipids may have resulted in the capture of more protein‐bound drug in the intravascular compartment by TPE.…”