Pharmacokinetics of 5-[4-(2-Carboxyethylcarbamoyle) phenylazo] Salicylic Acid Disodium Salt Dihydrate (BX661A) (1) : Plasma Concentration in Rat after a Single Oral or Intravenous Administration

Abstract

Plasma levels of radioactivity, the unchanged drug and major metabolites were investigated in rats after a single oral or intravenous administration of ¹⁴C-BX661A (labeled at 5ASA moiety: ¹⁴C-BX661A (5ASA), labeled at 4ABA moiety: ¹⁴C-BX661A (4ABA)) and non-labeled BX661A.
1. After oral administration of ¹⁴C-BX661A to fasted rats, plasma levels of radioactivity showed 2 peaks with maximum time (T_max) at 30 min and 8-10 hr. Concentrations of the 1st peaks were same in both labeled compounds, however those of 2nd peaks were different from each other, plasma concentrations at 8-10 hr were higher in ¹⁴C-BX661A(5ASA) and those at 24 hr were higher in ¹⁴C-BX661A(4ABA).
2. Acetylation of 5ASA was saturated at the high dose, and that of 4ABA was saturated at the low dose.
3. After oral administration of BX661A to fasted female rats, plasma concentrations of the unchanged drug were lower than those of male rats.
4. After oral administration of BX661A to non-fasted male rats, concentrations of the unchanged drug, 5ASA and Ac 5ASA were lower than those of fasted rats.On the other hand, plasma concentration of 4ABA and Ac-4ABA were not influenced by diet.
5. After intravenous administration of BX661A to male rats, the unchanged drug was declined with T_1/2(α) of 6.0-6.2 min and T_1/2(β) of 21.8-28.6 min. On the other hand, metabolites were not detected during the first 2 hr.
6. After intravenous administration of BX661A to female rats, significant differences were observed in T_1/2(α) (male: 6.2 min, female: 3.4 min), K_el (male: 0.068/min, female: 0.143/min), CL (male: 0.015 l/min/kg, female: 0.025 l/min/kg) and AUC_{(0-2 hr)} (male: 179744 ng·/ml, female: 111370 ng·h/ml).