Comparative metabolism and elimination of acetanilide compounds by rat

1. ¹⁴C-labelled propachlor, alachlor, butachlor, metolachlor, methoxypropachlor and some of their mercapturic acid pathway metabolites (MAP) were given to rat either by gavage or by perfusion into a renal artery. MAP metabolites were isolated from bile and urine.

2. Rat gavaged with propachlor and methoxypropachlor eliminated ¹⁴C mostly in urine, whereas rat gavaged with alachlor, butachlor and metolachlor eliminated ¹⁴C about equally divided between urine and faeces. When bile ducts were cannulated, the gavaged rat eliminated most of the ¹⁴C in bile for all compounds. The amount of ¹⁴C in bile from the propachlor-gavaged rat was less than that for the other acetanilides, with the difference being in the urine.

3. The mercapturic acid metabolites 2-methylsulphinyl-N-(1-methylhydroxyethyl)-N-phenylacetamide and 2-methylsulphinyl-N-(1-methylmethoxyethyl)-N-phenylacetamide were isolated from the urine and bile of the methoxypropachlor-gavaged rat.

4. Bile was the major route for ¹⁴C elimination when MAP metabolites of alachlor, butachlor and metolachlor were perfused into a renal artery. Urine was the major route for ¹⁴C elimination when MAP metabolites of propachlor and methoxypropachlor were perfused. Mercapturic acid conjugates were major metabolites in bile and urine when MAP metabolites were perfused.

5. We conclude that alkyl groups on the phenyl portion of the acetanilide causes biliary elimination to be favoured over urinary elimination.