Determination of the effect of tridiphane on the pharmacokinetics of [14C]-atrazine following oral administration to male Fischer 344 rats. 1990

C Timchalk, and M D Dryzga, and P W Langvardt, and P E Kastl, and D W Osborne
Mammalian and Environmental Toxicology Research Laboratory, Dow Chemical Company, Midland, MI 48674.

The absorption, distribution, metabolism and excretion of [14C]-atrazine was studied in male Fischer 344 rats administered a 30 mg [14C]-atrazine/kg of body weight oral dose with or without pretreatment with a non-radiolabeled oral dose of 60 mg tridiphane/kg of body weight. The objective of this study was to determine whether tridiphane had any meaningful effect on the pharmacokinetics and/or metabolism of atrazine in the rat. The 14C plasma time-course exhibited a mono-exponential decrease with an absorption and elimination half-life of approximately 3 h and 11 h, respectively for both treatment groups. In addition, at 72 h after the administration of [14C]-atrazine, approximately 93% of the administered radioactivity was recovered and the primary route of excretion was via the urine (67%) for both treatment groups. The feces accounted for approximately 18% of the dose, and less than 10% remained in the carcass, skin, and red blood cells (RBCs). The urine excreted in the first 24 h post-dosing contained approximately 57% of the administered radioactivity for both treatment groups. There were no appreciable differences in the metabolite distribution between treatment groups, and the major urinary metabolite of atrazine was found to be 2-chloro-4,6-diamino-1,3,5-triazine (II; 64-67%). Additionally, S-(2-amino-4-methylethylamino-1,3,5-triazin-6-yl)-mercapturi c acid (V; 13-14%), and S-(2,4-diamino-1,3,5-triazin-6-yl)-mercapturic acid (III; 9%) were tentatively identified based upon similar HPLC retention times as seen with synthesized standards. These data indicate that there are no meaningful differences in the absorption, distribution, metabolism, and excretion between rats administered only [14C]-atrazine and those administered both tridiphane and [14C]-atrazine. Therefore, it can be concluded that tridiphane has no meaningful effect on the pharmacokinetics and/or metabolism of atrazine in the rat.

UI MeSH Term Description Entries
D008297 Male Males
D008401 Gas Chromatography-Mass Spectrometry A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds. Chromatography, Gas-Liquid-Mass Spectrometry,Chromatography, Gas-Mass Spectrometry,GCMS,Spectrometry, Mass-Gas Chromatography,Spectrum Analysis, Mass-Gas Chromatography,Gas-Liquid Chromatography-Mass Spectrometry,Mass Spectrometry-Gas Chromatography,Chromatography, Gas Liquid Mass Spectrometry,Chromatography, Gas Mass Spectrometry,Chromatography, Mass Spectrometry-Gas,Chromatography-Mass Spectrometry, Gas,Chromatography-Mass Spectrometry, Gas-Liquid,Gas Chromatography Mass Spectrometry,Gas Liquid Chromatography Mass Spectrometry,Mass Spectrometry Gas Chromatography,Spectrometries, Mass-Gas Chromatography,Spectrometry, Gas Chromatography-Mass,Spectrometry, Gas-Liquid Chromatography-Mass,Spectrometry, Mass Gas Chromatography,Spectrometry-Gas Chromatography, Mass,Spectrum Analysis, Mass Gas Chromatography
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D004852 Epoxy Compounds Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS. Epoxide,Epoxides,Epoxy Compound,Oxiranes,Compound, Epoxy,Compounds, Epoxy
D004988 Ethers, Cyclic Compounds of the general formula R-O-R arranged in a ring or crown formation. Cyclic Ether,Cyclic Ethers,Ether, Cyclic
D006540 Herbicides Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses (POACEAE), and woody plants. Some plants develop HERBICIDE RESISTANCE. Algaecide,Algicide,Herbicide,Algaecides,Algicides

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