Meicelin Mechanism of Action

PHARMACOLOGY: In vitro Antibacterial Activity: MEICELIN has a broad antibacterial spectrum against gram-positive and gram-negative bacteria, especially Escherichia coli, Klebsiella sp., Haemophilus influenzae, Proteus sp. and Bacteroides fragilis.
This substance shows an antibacterial activity not only in logarithmic phase but also in early stationary phase of bacterial growth. Even in sub-MIC (minimum inhibitory concentration), it shows quick bactericidal and bacteriolytic action. In vivo antibacterial activity of the substance is stronger than that expected from MIC.
This substance is stable to beta-lactamases produced by various bacteria such as Escherichia coli, Proteus sp. and Bacteroides fragilis.
Mechanism of Action: MEICELIN inhibits the bacterial cell wall synthesis because of its high affinity for penicillin-binding protein, a usual action site of beta-lactams. It also combines with peptidoglycan, i.e., it inhibits bacterial peptidoglycan-lipoprotein binding. Therefore, it promotes bacteriolysis and shows a strong bactericidal activity in a short time.
CLINICAL STUDIES: The results of open clinical and comparative trials (respiratory and urinary tract infections) are summarized as follows: In a total of 1,776 patients for clinical efficacy evaluation, the efficacy rate was 73.3% (1,302/1,776). The efficacy rates against main diseases were as follows: See Table 2.

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PHARMACOKINETICS: Serum concentration: Healthy adults: The serum concentration of the product after intravenous injection (iv) or intravenous drip infusion (div) to adult males with normal renal function was dose-dependent. (See Figure 1 and Table 3.)

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Children: Intravenous injection: The serum concentration of the product after intravenous injection to children (n=9) was dose-dependent. (See Figure 2 and Table 4.)

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Intravenous drip infusion: The serum concentration of the product after 1-hour intravenous drip infusion at a dose of 40 mg/kg or 20 mg/kg was also dose-dependent. (See Figure 3 and Table 5.)

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Patients with renal impairment: The serum concentration of the product after intravenous injection of 0.5 or 1 g to patients with impaired renal function showed a tendency toward continuously high values and prolonged serum half-life depending on the degree of their impairment. (See Figure 4 and Table 6.)

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Distribution: Body fluids and tissue concentrations: When 1 g was administered by intravenous drip infusion to patients suffering from chronic bronchitis, the sputum concentration was 0.38 to 0.48 μg/ml.
When 1 g was administered by intravenous injection to patients suffering from peritonitis, the ascites concentration was 13.4 to 139.5 μg/ml. When 20 mg/kg was administered by intravenous injection to child patients suffering from peritonitis, it was 17.9 to 63.2 μg/ml.
When 1 g was administered by intravenous injection to patients who received panhysterectomy, the concentration in endometrium, ovary and salpinx were 33.7 to 45.8 μg/ml.
When 1 g was administered by intravenous injection to patients with biliary tract diseases, the biliary concentration was 4.6 to 36.0 μg/ml.
Protein binding: The binding rate to human plasma protein as determined by ultrafiltration method was constant within the concentration range of 5 to 100 μg/ml, being about 61% (in vitro).
Metabolism: No metabolites having antibacterial activity have been found in man.
Excretion: Healthy adults: This substance is excreted mainly from the kidney. In adults with normal renal function, the urinary excretion rates are about 80% within 6 hours and about 90% within 12 hours after intravenous injection (n=3) or intravenous drip infusion (n=3) of a single dose of 1 g.
Patients with renal impairment: In patients with severely impaired renal function (Ccr < 10), the urinary excretion rate is about 10% within 24 hours after intravenous administration and in case of patients with moderately impaired renal function (Ccr=48), it is about 50% within 6 hours and about 63% within 12 hours.