Absorption, distribution, metabolism and excretion of p-bromophenylacetylurea in the female rat.
1. This study has investigated absorption, distribution, metabolism and excretion of p-bromophenylacetylurea (BPAU) in the F344 female rat. BPAU and its metabolites were determined by HPLC. 2. Following a single p.o. dose of 150 mg/kg BPAU, the absorbed fraction of dosed BPAU was 65.9% and its half-life in the blood was 9.4 h. The relative distribution of BPAU (tissue/serum ratio) at 6 h (peak time point) after a single i.p. dose of 150 mg/kg BPAU was spinal cord (4.6+/-0.2) > liver (3.7+/-0.1) > brain (2.9+/-0.1) (mean+/-SD, n = 5), and they were significantly different from each other (p < 0.05). BPAU in spinal cord reached the highest level. 3. Absorbed BPAU was metabolized in vivo into three major metabolites. N'-hydroxy-p-bromophenylacetylurea (M1) was a dominant metabolite in tissues, whereas 4-(4-bromophenyl)-3-oxapyrrolidine-2,5-dione (M2) reached a high concentration in blood. N'-methyl-p-bromophenylacetylurea (M3) was mainly found in the urine. All three metabolites were excreted via the urine and together accounted for 87% of absorbed BPAU. 4. This study provides a basic understanding of BPAU absorption, distribution, metabolism and elimination in rat.
Xu
J
J
Faculty of Applied Sciences, University of the West of England, Bristol, UK. Jinsheng.Xu@uwe.ac.uk
Purcell
W M
WM
Ray
D E
DE
D000284:Administration, Oral; D000818:Animals; D001921:Brain / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects; D008956:Models, Chemical; D051381:Rats; D011916:Rats, Inbred F344; D013116:Spinal Cord / Q000187:drug effects; D013997:Time Factors; D014018:Tissue Distribution; D014508:Urea / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine
C004506:4-bromophenylacetylurea; D014508:Urea