Elimination of methoxyacetic acid and ethoxyacetic acid in rat

Abstract

1. The pharmacokinetics of methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) have been determined in the male and female rat following bolus intravenous administration at 100 mg/kg. The plasma-concentration data of MAA fitted well to a one-compartment model, and the plasma-concentration data of EAA to a two-compartment model. 2. The elimination half-life of MAA estimated from plasma data was higher in females (18.6 ± 2.0 h) than in males (13.2 ± 0.4 h). There was no difference in the elimination half-lives estimated from urine data. The apparent volume of distribution was lower in the male than in the female rat estimated from plasma data only, while AUC, total and non-renal clearances and the relative amount MAA excreted unchanged in urine was similar in the male and female rat. 3. Clearance of EAA is higher than of MAA, and this appears as a result of metabolic capacity. The elimination half-lives of EAA were similar in the male and female rat, 9.4 ± 3.7 and 10.5 ± 2.6 h respectively. AUC was higher in the female compared with the male rat. The fraction of EAA eliminated during the distribution phase was 44.0 ± 15.4 and 41.0 ± 17.4% in the male and female rat respectively. The initial volume of distribution, the apparent volume of distribution, total and non-renal clearance are higher in the male compared with the female rat.