| Popis: |
The absorption, distribution, metabolism and excretion of Ritipenem acoxil (RIPM-AC), an oral prodrug of antibiotic Ritipenem (RIPM), were investigated in rats and dogs after a single oral administration of 14C-RIPM-AC. 1. A fter oral administration of 14C-RIPM-AC to male rats at a dose of 30 mg/kg, the radioactivity level peaked at 30 min in blood, indicating rapid absorption from intestinal tract. In the in situ loop study, RIPM-AC was mainly absorbed from proximal region of the small intestine. About 50% of the administered dose was absorbed. The feeding condition did not affect the absorption. RIPM-AC was not detected in the plasma. RIPM-AC was hydrolyzed to RIPM in the intestinal tract. Maximum concentration of RIPM was found at 30 min. 2. The radioactivity levels in the kidney, urinary bladder and intestine were high and those in the other tissues were lower than 71% of that in the plasma. RIPM was detected by bioassay in the kidney and plasma up to 30 min but not in the lung and liver. The binding ratio of radioactivity to plasma proteins was 55% at 30 min after administration and increased with time. Irreversible binding also increased. The elimination of radioactivity from the fat, central nervous system, thyroid gland, adrenal gland, spleen, thymus, skeletal muscle, bone marrow and brown fat was slow. 3. The excretion of radioactivity in the urine, feces and expired air was completed within 48 hr after administration of 14C-RIPM-AC to male rats at a dose of 30 mg/kg, accounting for 47.7, 40.6 and 7.1% of the dose within 120 hr, respectively. The biliary excretion of radioactivity was 1.2% of the dose. RIPM accounted for more than 50% of the radioactivity excreted in the urine within 4 hr. 4. The metabolic fate of RIPM-AC was dose-dependent ranging from 10 to 100 mg/kg and independent of sex. 5. Species differences were observed in the metabolic fate of RIPM-AC between rats and dogs. |
