Metabolism and disposition of 2-methoxy-4-nitroaniline in male and female Harlan Sprague Dawley rats and B6C3F1/N mice.
The disposition of 2-Methoxy-4-nitroaniline (MNA) was investigated in male and female Harlan Sprague Dawley rats and B6C3F(1)/N mice following oral, intravenous, and dermal exposure to [(14)C]MNA at 2, 15, or 150 mg/kg. Clearance of MNA was investigated in male and female rat, mouse, and human hepatocytes.        MNA was cleared slowly in hepatocytes from rat (t(1/2) = 152-424 min) and human (t(1/2) = 118-403 min) but faster in mouse (t(1/2)= 70-106 min).        MNA was well-absorbed in rats and mice following oral administration and eliminated chiefly in urine (rats, 75-79%; mice, 55-68%) 72 h post dosing. Less than 1% of the radioactivity remained in tissues at 72 h. MNA was poorly absorbed following dermal application in rats (5.5%) and mice (10%) over 24 h.        The major pathway of metabolism of MNA was via hydroxylation of the phenyl ring to form 6-hydroxy MNA; major metabolites detected were sulfate and glucuronide conjugates of 6-hydroxy MNA.        Following oral administration, the percent of total radioactivity bound in tissues bound was highest in liver (43%) and red blood cells (30%), whereas the radioactivity bound to DNA was highest in cecum (160 pmol/mg DNA).
RTI International, Research Triangle Park, NC, USA.
James M
JM
Mathews
Qiao
Q
Zhan
Amy S
AS
Etheridge
Purvi R
PR
Patel
Sherry R
SR
Black
Troy T
TT
Banks
Timothy R
TR
Fennell
Rodney W
RW
Snyder
Jason P
JP
Burgess
Stephen D
SD
Warren
Inok
I
Surh
Suramya
S
Waidyanatha
D000814:Aniline Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes / Q000008:administration & dosage; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism; D004333:Drug Administration Routes; D005260:Female; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D009574:Nitro Compounds / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000652:urine; D011851:Radioactivity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D014018:Tissue Distribution / Q000187:drug effects
D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D009574:Nitro Compounds; D004247:DNA; C582628:2-methoxy-4-nitroaniline