Document Detail

Formulation-dependent toxicokinetics explains differences in the GI absorption, bioavailability and acute neurotoxicity of deltamethrin in rats.
MedLine Citation:
PMID:  17448586     Owner:  NLM     Status:  MEDLINE    
The acute neurotoxicity of pyrethroid insecticides varies markedly with the dosage vehicle employed. The objective of the present study was to assess the influence of two common vehicles on the bioavailability and toxicokinetics (TK) of a representative pyrethroid insecticide, deltamethrin (DLM), to determine whether the vehicles influence toxic potency by modifying the chemical's TK. Adult, male Sprague-Dawley rats were administered DLM iv or po, either by dissolving it in glycerol formal (GF) or by suspending it in Alkamuls (AL). Groups of rats received 10mg DLM/kg by gavage in each vehicle, as well as 2 mg/kg in GF or 10mg/kg in AL by iv injection. Serial blood samples were collected over 96 h and analyzed for their DLM content by HPLC. In a second experiment, plasma, brain, fat, liver and lung DLM concentrations were measured 2h after giving 10mg DLM/kg orally in GF or AL. In a third experiment rats received 2 or 10mg DLM/kg iv in AL or 2mg DLM/kg iv in GF. Lung DLM content was determined 15 min post injection. DLM particle size in both formulations was measured under a phase contrast microscope. DLM appeared to be completely dissolved in GF, while particle size ranged from <5 to >50 microm in AL. The bioavailability of DLM in the aqueous AL suspension was approximately 9-fold lower than in GF (1.7% versus 15%). Blood C(max) (0.95+/-0.27 versus 0.09+/-0.01 microg/ml) and AUC(0)(48h) (5.49+/-0.22 versus 0.61+/-0.14 microg.h/ml) were markedly higher in the GF gavage group. Tissue DLM levels were also significantly higher in the GF animals at 2h. The 10mg/kg po and 2mg/kg iv doses of DLM in GF produced moderate salivation and slight tremors. Rats receiving the insecticide in AL were asymptomatic. IV injection of the AL suspension resulted in trapping of much of the dose in the pulmonary capillaries. As anticipated, the injected suspension had a longer half-life and slower clearance than did the GF formulation. In summary, limited dissolution of the highly lipophilic DLM particles in the AL suspension severely limited DLM's GI absorption, bioavailability, target organ deposition and acute neurotoxic potency.
Kyu-Bong Kim; Sathanandam S Anand; Srinivasa Muralidhara; Hyo J Kim; James V Bruckner
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-02-28
Journal Detail:
Title:  Toxicology     Volume:  234     ISSN:  0300-483X     ISO Abbreviation:  Toxicology     Publication Date:  2007 May 
Date Detail:
Created Date:  2007-04-30     Completed Date:  2007-07-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0361055     Medline TA:  Toxicology     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  194-202     Citation Subset:  IM    
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30605, USA.
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MeSH Terms
Acute Disease
Area Under Curve
Biological Availability
Chemistry, Pharmaceutical
Insecticides / chemistry,  pharmacokinetics*,  toxicity*
Intestinal Absorption / physiology
Neurotoxicity Syndromes / physiopathology*
Nitriles / chemistry,  pharmacokinetics*,  toxicity*
Particle Size
Pyrethrins / chemistry,  pharmacokinetics*,  toxicity*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Insecticides; 0/Nitriles; 0/Pyrethrins; 52820-00-5/decamethrin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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