Toxicokinetics, recovery, and metabolism of metamitron in goat
2003
Toxicokinetic behavior and metabolism studies of metamitron and its effect on the cytochrome P450 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 microgram mL-1), maximum at 4 h (84.3 ± 8.60 microgram mL-1) and minimum (14.6 ± 1.67 microgram 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 t1/2β (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), Fc (0.55 ± 0.01), ClB (0.15 ± 0.00 L kg-1 h-1), and K21 (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 ClR compared to ClH 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 P450 content of liver microsomal pellet of goat, suggesting oxidative deamination of metamitron.
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