Disposition of 7432-S in rats (I)

Abstract

The absorption, excretion and metabolism of 7432-S were studied in male and female rats using 14C-labeled compound. 14C-7432-S, dissolved in phosphate buffer (10 mg/ml), was administered orally or intravenously to rats at 20 mg/kg or 5 mg/kg, respectively. When the drug was given orally, the plasma level of radioactivity reached maximum (9.18μg equivalent/ml) 30 min after the administration, then declined rapidly. Most of the plasma radioactivity was present as unchanged 7432-S and concentrations of 7432-S-trans were extremely low. Pharmacokinetic parameters of 7432-S after oral administration were as follows: Tmax was 24 min, Cmax was 7.44μg/ml and t1/2 was 52 min. The t1/2 after intravenous administration was 17.3 min. 7432-S was not absorbed from the stomach, caecum and colon, but from the small intestine. The rate of absorption in rats was estimated to be 50% of the dose from the sum of urinary and biliary excretions. After oral administration, 47% of the dose was excreted in the urine and 46% in the 4eces within 24 h. Unchanged 7432-S accounted for most of the urinary radioactivity and metabolites only for a small percentage. Biliary excretion of radioactivity in bile-duct cannulated rats was 8% of the dose after oral adminstration and 12% after intravenous administration within 24 h. Most of the radioactivity after oral administration was due to 7423-S, with 1.2% of B-1. © 1989, Japanese Society of Chemotherapy. All rights reserved.