Toxicokinetics, recovery, and metabolism of metamitron in goat

Toxicokinetic behavior and metabolism studies of metamitron and its effect on the cytochrome P(450) content of liver microsomal pellet were carried out in black Bengal goats after a single oral administration at 278 mg kg(-1) and consecutive oral administration of 30 mg kg(-1) for 7 days. Metamitron was detected in the blood sample at 0.08 h (12.0 +/- 0.87 microg mL(-1)), maximum at 4 h (84.3 +/- 8.60 microg mL(-1)) and minimum (14.6 +/- 1.67 microg mL(-1)) at 36 h blood sample after a single oral administration. The absorption rate constant was 0.69 +/- 0.09 h(-1). The Vd(area) (2.00 +/- 0.08 L kg(-1)) and t(1/2)beta (8.98 +/- 0.70 h) values suggested wide distribution and long persistence of the compound in the body. The values of T approximately B (0.80 +/- 0.04), F(c) (0.55 +/- 0.01), Cl(B) (0.15 +/- 0.00 L kg(-1) h(-1)), and K(21) (0.41 +/- 0.03 h(-1)) suggested that metamitron retained in the blood compared to that in the tissue. Maximum concentration of metamitron residue was found in the adrenal gland followed by bile on day 4 of single oral administration. The higher Cl(R) compared to Cl(H) value indicated the excretion of the major portion (34-40%) through urine compared to feces (20-26%). Maximum concentrations of metamitron and its metabolite, deaminometamitron, were excreted through urine and feces at 48 and 24 h samples, respectively. The recovery of metamitron including its metabolite in terms of parent compound varied from 69.3 to 80.1%, of which contribution of metabolite in terms of parent compound varied from 53.1 to 63.0%. Repeated oral administration of metamitron at 30 mg kg(-1) for 7 days caused induction of the cytochrome P(450) content of liver microsomal pellet of goat, suggesting oxidative deamination of metamitron.