Biapenem (LJC 10627) is a carbapenem antibiotic for injection developed by Lederle company of Japan and cyanamide company of the United States in 1989. At present, phase III clinical study has been completed in Japan and it is waiting to be approved for marketing. The most prominent feature of this product is 1 β - methylcarbapenem with bicyclotriazole on the 2-s position. The structure-activity relationship study showed that the presence of quaternary ammonium cation center in the side chain was the key to affect the permeability of outer membrane. The inhibition activity of the product against Pseudomonas aeruginosa and anaerobic bacteria was 2-4 times stronger than that of imipenem, the activity of inhibiting drug-resistant Pseudomonas aeruginosa was 4-8 times stronger than meropenem, and it was more effective than ceftazidime in Acinetobacter and anaerobic bacteria. The following comparison of apenem's pharmacology, efficacy, antibacterial effect and clinical research are briefly introduced.
As a new generation of penicillin antibiotics, biapenem has the pharmacological activity of general carbapenem antibiotics. The results showed that biapenem had no significant effect on spontaneous activity, drug-induced hypnosis or electric shock, but had no significant effect on inflammatory pain and intrinsic temperature of experimental rats. The results showed that the brain wave and respiration of rabbits did not change significantly after 300 mg / kg intravenous injection, while mild blood pressure and bradycardia were induced by intravenous injection of 100mg / kg in anesthetized dogs, but there was no effect on 30mg / kg. 100 μ g / ml biapenem could induce the relaxation and contraction of the ileum of brain body guinea pigs, but had no significant effect on the plasma prothrombin time and partial activated prothrombin time in rabbits.
The Cmax, AUC, half-life and urinary excretion were 18.9 μ g / ml, 27.2 μ g.h/ml, 1.1 h and 61.5%, respectively. Yamashita Xianzhao et al. Injected 14C biapenem intravenously into dogs and monkeys at a dose of 10mg / kg, respectively. The blood concentration and excretion of 14C biapenem were determined. The results showed that the plasma concentration was 43.7 μ g / ml in dogs, 48.3 μ g / ml in monkeys, the half lives were 26.2 and 9.9 h, AUC were 58.8 and 62.2 μ g · H / ml, respectively; there was no significant difference in pharmacokinetic parameters between single intravenous administration and multiple administration. The drug is stable in vivo. It mainly exists in blood and urine and excreted through urine. The 24-hour urine recovery rate is 99.3%, of which 77% is the original drug. The drug is widely distributed in various organs and tissues, of which the highest concentration is found in kidney and bladder, followed by skin, lung and liver, and only trace amount exists in brain and spinal cord.
In vitro antibacterial activity
The results showed that biapenem had broad-spectrum and strong antibacterial activity against G + bacteria, G-bacteria and anaerobic bacteria. The MIC90 range of the product against 456 strains of G + bacteria was 0.006 ~ 3.13 μ g / ml; the MIC90 range of 1145 G-bacteria was 0.1 ~ 3.13 μ g / ml, which was twice as strong as imipenem; the MIC90 range of most anaerobic bacteria was 0.05 ~ 1.56 μ g / ml. Biapenem has broad-spectrum antibacterial activity, and its antibacterial activity is similar to imipenem and meropenem, but stronger than laoxycef and ceftazidime. The mic value of this product was similar to that of MBC. When the concentration of MIC was higher than mic, the morphology of Pseudomonas aeruginosa and E. coli were changed. Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes and pneumococci are highly sensitive to this drug, but methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis are also resistant to the drug. In addition, the product has good antibacterial activity against Bacteroides fragilis, and its MIC90 is 1.56 μ g / ml. Studies by Murakami and others showed that the antibacterial activity of the product against clinically isolated G + bacteria and Enterobacteriaceae bacteria was similar or slightly weaker than that of imipenem, but the activity to Enterobacteriaceae was stronger than imipenem; the antibacterial activity of this product against non fermentative G-bacteria, especially Pseudomonas aeruginosa and GM resistant Pseudomonas aeruginosa, was 2 times stronger than imipenem.
In vivo antibacterial activity
The in vivo antibacterial activity of this product is similar to imipenem and other penicillins, and it has good protective effect on mice infected with G + bacteria or G-bacteria, especially for mice infected with Pseudomonas aeruginosa than imipenem / CST; even for the mixed infection of Pseudomonas aeruginosa and Escherichia coli, the product also has good effect.
Shino Wuzhi and pepeostn studied the protective effect of this product on Pseudomonas aeruginosa, Serratia or Acinetobacter calcoacetate infection in mice. The results showed that the efficacy of the product was better than imipenem / CST, meropenem and other reference drugs.
Clinical research shows that this product is used to treat acute and chronic infections caused by G + bacteria, G-bacteria and anaerobic bacteria which are sensitive to this product. In a clinical trial of 1340 cases of various infectious diseases, 1255 cases can be evaluated and 1101 cases are effective. The total effective rate is 87.7%. In addition, there were 485 cases of internal infection (mainly respiratory infection). After using this product, 434 cases were effective, the effective rate was 89.5%, the effective rate of pneumonia was 89.9% (266 / 296), the effective rate of chronic bronchitis was 94.1% (48 / 51), and the effective rate of secondary infection of bronchiectasis was 92.1% (35 / 38). The effective rate was 79.6% (179 / 225) for urinary system infection (mainly complicated urinary tract infection), 83.3% for simple pyelonephritis and 100% for acute prostatitis. Among 133 cases of gynecological infection, 51 cases were intrauterine infection, 50 cases were effective (98%), 31 cases were adnexitis, 28 cases (90.3%) were effective, and it had significant effect on other gynecological infections. At the same time, biapenem has a significant effect on other infections, such as sepsis, endocarditis, etc