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Therapeutic effect on experimental infection in mice: The therapeutic efficacy of biapenem against intraperitoneal infection caused by various bacteria, mixed intraperitoneal infection caused by E. coli and P. aeruginosa, P. aeruginosa infection in leucopenic mice, respiratory infections caused by K. pneumoniae, P. aeruginosa and penicillin-resistant S. pneumoniae, and urinary tract infections caused by E. coli and P. aeruginosa in mice was equivalent to or better than that of imipenem.
Mechanism of action: Biapenem inhibits bacterial cell wall synthesis (by blocking the murein crosslink formation). In particular, biapenem exhibits high affinity for penicillin binding protein (PBP) 1 and 4 in MSSA and PBP 2 and 4 in E. coli and P. aeruginosa.
Pharmacokinetics: Plasma concentration: The plasma concentrations in healthy adults (n=5) after a single administration of 150 mg, 300 mg and 600 mg of biapenem by intravenous drip infusion over 60 minutes are shown in Figure 1, and a dose dependency was observed. When biapenem was administered by repeated intravenous drip infusion, the pharmacokinetics were almost similar to those obtained after a single intravenous drip infusion and no accumulation of biapenem was observed. (See Figure 1 and Table 1.)
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Click on icon to see table/diagram/imageBody fluid and tissue distribution: When 300 mg of biapenem was administered once by intravenous drip infusion over 30 or 60 minutes, the maximum concentration in the dead space fluid in the pelvis was 9.6 μg/mL. The concentrations in the sputum within 6 hours after administration ranged from 0.1 to 2.5 μg/mL.
Metabolism: No metabolites were detected in the plasma following a single intravenous drip infusion of 150, 300 and 600 mg of biapenem, or repeated intravenous drip infusion of 300 and 600 mg in healthy adults (n=5). When biapenem was administered once by intravenous drip infusion or administered by repeated intravenous drip infusion, 9.7 to 23.4% of its total metabolites were excreted in the urine. These metabolites showed no antibacterial activity.
Excretion: When 150, 300 and 600 mg of biapenem were administered once by intravenous drip infusion over 60 minutes to healthy adults (n=5), the average urinary concentrations of biapenem were, 325.5, 584.8 and 1,105.1 μg/mL, respectively at 0-2 hours after administration, and 2.4, 4.7 and 21.4 μg/mL, respectively at 8-12 hours after administration. The cumulative urinary excretion rates were 62.1%, 63.4% and 64.0%, respectively, at 0-12 hours after administration.
Plasma concentrations in patients with renal function impairment: When 300 mg of biapenem was administered once by intravenous drip infusion over 60 minutes to patients with renal function impairment (n=3), biapenem disappearance from the plasma was confirmed to be delayed as renal function decreased. (See Figure 2 and Table 2.)
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Click on icon to see table/diagram/imageWhen biapenem was administered twice daily for 7 days, 14 times in total, by repeated intravenous drip infusion over 30 minutes to patients with moderate renal function impairment with a creatinine clearance creatinine clearance of about 50 mL/min, no accumulation of biapenem was observed in the plasma or urine.
Biapenem disappearance from the plasma was confirmed to be delayed when hemodialysis was not performed, following administration of 300 mg of biapenem by intravenous drip infusion over 60 minutes to patients with renal function impairment requiring hemodialysis (n=5). (See Figure 3 and Table 3.)
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Click on icon to see table/diagram/image
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