Bleocin Mechanism of Action

Pharmacology: Pharmacodynamics: Antineoplastic activity: In vitro: In HeLaS₃ cells, Ehrlich ascites liver carcinoma and Yoshida sarcoma cells, etc., inhibition of DNA and protein syntheses and growth inhibition of the cells were observed.
In vivo: Disappearance of spontaneous lympho-sarcoma in dogs was observed.
Mechanism of Action: The mechanism of action of bleomycin is the inhibitory effect on DNA synthesis and the DNA strand splitting.
Clinical Studies: Results of Domestic Clinical Studies: The response rates for each disease are summarized as follows: (See Table 2.)

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Results of Reevaluation (1989): Response rates by diseases are shown as follows. For skin cancer, the response rate is higher than the rate at the time of approval, since Bleocin has mainly been used concomitantly with other drugs. Evaluation of efficacy for thyroid cancer was performed in only 3 patients. For other diseases, the results of reassessment were almost the same as those at the time of approval. (See Table 3.)

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Pharmacokinetics: Pharmacokinetics and metabolism: Pharmacokinetics of Bleocin is characteristic and shows the main component, bleomycin A₂, is highly distributed to the skin. Assays for the biological activity of bleomycin distributed to each tissue show that Bleocin is active form in the skin, lung, kidney, and bladder, while inactive form in other tissues including liver, spleen, etc. These findings demonstrate that Bleocin has effects particularly on skin cancer and head and neck cancer, without causing hematopoietic disorder.
When bleocin is administered intravenously at 15 mg (potency) in adults, the blood concentration reaches 3 μg/mL immediately after administration and < 0.5 μg/mL by 1 hour later. When Bleocin is administered intramuscularly, the blood concentration reaches a peak value by approximately one third of the value for intravenous administration, and then gradually decreases. The urinary excretion rate was 38.3% for intravenous administration and 19.2% for intramuscular administration up to 24 hours after administration. When surgery was performed 30-37 minutes after intravenous administration of Bleocin at 15 mg (potency) in 3 patients with penile cancer or penis carcinoma, the blood concentration was 0.69-0.94 μg/mL and intratumoral concentration was 0.08-0.49 μg/g. When surgery was performed 7 days after intravenous administration of Bleocin at a total dose of 300 mg (potency) in a patient with orchioncus, the concentration was 430 μg/g in the skin and 4 μg/g in the tumor. The urinary excretion rate of the unchanged drug was 68%. Systemic clearance was 1.1 mL/min/kg, distribution volume was 0.27 L/kg, and half-life in blood was 3.1 hours.
Blood concentration: The figure as follows shows the blood concentration when bleomycin is administered intravenously or intramuscularly at a dose of 15 mg (potency) in 4 cancer patients. (See Figure.)

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