Absorption, Distribution and Excretion
Following oral administration to rats, the drug is rapidly excreted. The main component in feces is unmetabolized famoxaone; monohydroxylated (4'-phenoxyphenyl) and dihydroxylated (4-phenylamino) famoxaone are the main fecal metabolites. Heterocyclic cleavage products were detected in urine. Low tissue residues were observed in goats and hens; most of the administered famoxaone (approximately 60%) was unmetabolized and excreted in feces. The metabolic process is complex, involving hydroxylation, cleavage of the oxazolidinedione-aminophenyl bond, cleavage of the phenoxyphenyl ether bond, and ring opening of the oxazolidinedione ring. Ten groups of Cr1:CD/BR (Sprague-Dawley) albino rats, 4 or 5 males and females per group, were administered [14C-PA]DPX-JE874 by gavage at doses of 5 or 100 mg/kg. One group (Group G), consisting of 5 males and females per group, received unlabeled DPX-JE874 via gavage for 14 consecutive days prior to the administration of the radiolabeled dose. The other two groups (Group B (4 males and females per group) and Group E (5 males and females per group)) received a single gavage administration of [14C-POP]DPX-JE874 at a dose of 100 mg/kg. In Groups A, B, and C: the absorption half-life of [14C-PA]DPX-JE874 in whole blood and plasma increased from 0.8–1.2 hours to 3.5–7.1 hours as the dose increased from 5 mg/kg to 100 mg/kg. The absorption half-life of [14C-POP]DPX-JE874 at a dose of 100 mg/kg was 0.4–1.4 hours. Compared to plasma, the elimination half-life of [14C-PA]DPX-JE874 in whole blood is 2–3 times slower (indicating its binding to erythrocytes). [14C-POP]DPX-JE874 showed no signs of binding to erythrocytes. In groups D, E, F, and G: at 120 hours post-administration, no accumulation of [14C-PA]DPX-JE874 residues in organs and tissues was observed in either the 5 mg/kg or 100 mg/kg dose groups. The highest radioactivity (< 2 ppm) was observed in the adipose tissue of animals in the [14C-POP]DPX-JE874 treatment group (Group E, 100 mg/kg). Slight increases in 14C residue levels (< 2 ppm) were also observed in the gonads, uterus, adrenal glands, and bone marrow (possibly related to adipose tissue adhesion). Within 24 hours post-administration, over 75% of the radiolabeled material was excreted in feces, and less than 10% in urine. There were no significant differences in elimination curves between single-dose (D, E, and F) and multiple-dose (G) administration, between different sexes, and between [14CPA]DPX-JE874 and [14C-POP]DPX-JE874. …In groups H and I: at 5 hours (5 mg/kg) and 14 hours (100 mg/kg) post-administration, [14C-PA]DPX-JE874 residues were mainly distributed in the liver and adipose tissue. At 36 hours (5 mg/kg) and 48 hours (100 mg/kg) post-administration, the liver was the only tissue with a slightly elevated residue level. Seven male and seven female rats in each group were given a single oral gavage dose of 5 mg/kg of [14C-PA]DPX-JE874 or [14C-POP]DPX-JE874. Animals underwent biliary and duodenal cannulation surgery 3 days prior to treatment. Bile was continuously collected and samples were taken at 1, 3, 6, 10, 16, 24, 36, and 48 hours after administration. Urine and feces were collected at 12, 24, and 48 hours after administration. After the last collection of urine and feces, cage flushing fluid was collected and analyzed. Blood was collected from all animals at the end of the experiment (48 hours after treatment). The carcasses were homogenized and analyzed for radioactivity. Within 1 to 10 hours after administration, 30% to 39% of the radiolabeled material was excreted in bile. Male animals excreted [14C-POP]DPX-JE874 (39%) more than [14C-PA]DPX-JE874 (31%). The mean urinary excretion of the radiolabeled material was 2% to 6% of the administered dose. 56% to 65% of the administered dose was excreted in feces. At the end of the experiment, 0.22% and 0.31% of the administered dose were detected in the blood of male and female animals treated with [14C-PA]DPX-JE874, respectively. 0.03% of the administered dose was detected in the blood of both male and female animals treated with [14C-POP]DPX-JE874. The mean concentration of the radiolabeled substance in the carcass ranged from 0.4% to 3.0%. Six male beagle dogs received a single oral gavage administration of [14C-PA]DPX-JE874 at a dose of 15 mg/kg. Three animals (Group A) were used for pharmacokinetic sampling (sacrificed 96 hours after administration), and another three animals (Group B) were used to assess tissue distribution at the peak plasma concentrations observed in Group A (sacrificed 2 hours after administration). The last animal served as an excipient control (Group C) (sacrificed 96 hours after administration). In Group A dogs, the average recovery rate of radioactive material in urine was 7.67% within 96 hours after administration, 70.3% in feces, and 0.74% in cage cleaning and wiping solutions. The average peak excretion of radioactive material in urine occurred between 24 and 48 hours after administration, while in feces it occurred between 12 and 24 hours. The average concentration of radioactive material in plasma peaked at 1.53 ppm 2 hours after administration, and in erythrocytes at 0.626 ppm 4 hours after administration. At 96 hours, the radioactive concentrations in plasma and erythrocytes were 0.597 ppm and 0.648 ppm, respectively. At 96 hours of sacrifice, the highest average radioactive concentrations were detected in the liver (1.34 ppm) and mesenteric fat (0.945 ppm). The average concentrations in aqueous humor, eyeball, and eye remnants were 0.091 ppm, 0.135 ppm, and 0.173 ppm, respectively. In group B animals (euthanized after 2 hours), the highest mean radioactive concentrations were detected in the liver (4.45 ppm), mesenteric fat (2.80 ppm), plasma (0.999 ppm), and erythrocytes (0.413 ppm). Residual levels in aqueous humor, intraocular fluid, and intraocular residues were 0.061 ppm, 0.106 ppm, and 0.131 ppm, respectively. For more complete data on the absorption, distribution, and excretion of famoxazone (6 items), please visit the HSDB record page. Metabolism/Metabolites Hydroxylation of the two benzene rings at the para position is the primary metabolic pathway. ...Four or five Crl:CD/BR (Sprague-Dawley) albino rats (half male and half female) were administered a single oral gavage dose of 5 or 100 mg/kg of [14C-PA]DPX-JE874.../or/a single oral gavage dose of 100 mg/kg of [14C-POP]DPX-JE874. Three radioactive components were detected in the feces of both [14C-PA] and [14C-POP] treated animals. Unmetabolized 14C-DPX-JE874 was the major component. The other two components were monohydroxylated (IN-KZ007) and para-hydroxylated (IN-KZ534) DPX-JE874. A major radioactive component (sulfate conjugate) was detected in the urine of [14C-POP] treated animals. The major metabolite in the urine of [14C-PA] treated animals was consistent with 4-acetoxyaniline (HPLC).

[1]. D T Likas, et al. Rapid Gas Chromatographic Method for the Determination of Famoxadone, Trifloxystrobin and Fenhexamid Residues in Tomato, Grape and Wine Samples. J Chromatogr A. 2007 May 25;1150(1-2):208-14.

5-Methyl-5-(4-phenoxyphenyl)-3-(phenylamino)-1,3-oxazolidine-2,4-dione belongs to the oxazolidinedione class of compounds. Its structure is similar to 1,3-oxazolidine-2,4-dione, except that the hydrogen atom on the nitrogen atom is replaced by a phenylamino group, and the hydrogen at the 5-position is replaced by a methyl group and a 4-phenoxyphenyl group. It is an aromatic ether, carbazide, and oxazolidinedione compound. Methoxythrone is an oxazolidinedione fungicide used to protect agricultural products from a variety of fungal diseases, including downy mildew and wilt on fruits, vegetables, tomatoes, potatoes, cucurbits, lettuce, and grapes. It is often used in combination with cymoxanil. Methoxythrone has low water solubility, a low risk of seepage into groundwater, and is non-volatile. It is not persistent in soil or water. Although its toxicity to mammals is low, there are still minor concerns about its bioaccumulation. It is considered a neurotoxin and is known to irritate the eyes and skin. It is highly toxic to fish and aquatic invertebrates, and moderately toxic to other aquatic organisms, earthworms, and bees.

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Mechanism of Action
Famoxaone is a potent inhibitor of mitochondrial electron transport, acting on complex III in the mitochondria of fungi, plants, and mammals… Its inhibitory site is cytochrome b within the Qo domain, thereby preventing electrons from being transferred from cytochrome b to cytochrome c1.

C22H18N2O4

374.39

374.126

131807-57-3

213032

Pale cream powder

1.3±0.1 g/cm3

491.3±55.0 °C at 760 mmHg

140.3-141.8ºC

250.9±31.5 °C

0.0±1.2 mmHg at 25°C

1.659

4.76

1

5

5

28

563

0

CC1(C2=CC=C(C=C2)OC3=CC=CC=C3)C(=O)N(C(=O)O1)NC4=CC=CC=C4

PCCSBWNGDMYFCW-UHFFFAOYSA-N

InChI=1S/C22H18N2O4/c1-22(16-12-14-19(15-13-16)27-18-10-6-3-7-11-18)20(25)24(21(26)28-22)23-17-8-4-2-5-9-17/h2-15,23H,1H3

3-anilino-5-methyl-5-(4-phenoxyphenyl)-1,3-oxazolidine-2,4-dione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 100 mg/mL (267.10 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.68 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.68 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)