Pharmacokinetics and Dosimetry of the Antiandrogen Vinclozolin after Oral Administration in the Rat

• DOI: 10.1093/toxsci/kfn167
• Publication Date: 2008-08-15T00:34:27Z
• Authors: Adolfo Sierra-San...; Gilberto Castañed...; Randy A. Harrison; Hugh A. Barton; Michael F. Hughes
• Keywords: Beagle

Vinclozolin (V) is a fungicide with antiandrogenic properties. To determine the pharmacokinetics and dosimetry of V, adult male rats were administered an oral dose V (100 mg/kg) in corn oil sacrificed over time after dosing. its metabolites analyzed serum tissues by high performance liquid chromatography/diode array detector/mass spectrometer. 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2), five other detected tissues. One metabolite was identified as 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). The mean concentration data for fitted to one-compartment model kinetic analysis. At 2 h, peaked; whereas only trace levels at 24 h (t(1/2 elim) = 3.6 h). all preferentially accumulated fat. M1 increased until 8 being least 2-fold higher than those this time, then declined t(1/2) 3.3 h. M5 main Serum 5-fold greater times. 48 remained 13.1 Liver kidney exhibited highest M5, M1. M2 3,5-dichloroaniline had lowest well absorbed, extensively metabolized widely distributed. most abundant metabolite, may be used exposure biomarker pharmacokinetic modeling. These results clarify relationship between toxicity tissue metabolites.