Pharmacology: Pharmacodynamics: Bleomycin is a basic, water-soluble glycopeptide with cytotoxic activity. The mechanism of action of bleomycin is believed to involve single-strand scission of DNA, leading to inhibition of cell division, of growth and of DNA synthesis in tumour cells.
Apart from its antibacterial and antitumour properties, bleomycin is relatively free from biological activity. When injected intravenously it may have a histamine-like effect on blood pressure and may cause a rise in body temperature.
Pharmacokinetics: Bleomycin is administered parenterally. After intravenous (IV) administration of a bolus dose of 15 x 103 IU/m2 body surface, peak concentrations of 1 to 10 IU are achieved in plasma. Following the intramuscular (IM) injection of 15 x 103 IU peak plasma concentrations of about 1 IU/mL have been reported. The peak plasma concentration is reached 30 minutes after an IM injection. Continuous infusion of bleomycin 30 x 103 IU daily, for 4 to 5 days, resulted in an average steady state plasma concentration of 100-300 milli IU/mL. After IV injections of bleomycin in a dose of 15 x 103 IU/m2 body surface, the area under the serum concentration curve is, on average, 300 milli IU x min x mL- 1.
Bleomycin is only bound to plasma proteins to a slight extent. Bleomycin is rapidly distributed in body tissues, with the highest concentrations in skin, lungs, peritoneum and lymph. Low concentrations are seen in the bone marrow. Bleomycin could not be detected in cerebrospinal fluid after intravenous injection. Bleomycin appears to cross the placental barrier.
The mechanism for bio-transformation is not yet fully known. Inactivation takes place during enzymatic breakdown by bleomycin hydrolase, primarily in plasma, liver and other organs and, to a much lesser degree, in skin and lungs. When bleomycin was administered as an IV bolus injection in a dose of 15 x 103 IU/m2 body surface, initial and terminal half-lives were 0.5 and 4 hours respectively. Given as a continuous intravenous infusion in a dose of 30 x 103 IU daily for 4 to 5 days bleomycin disappears from plasma with initial and terminal half-lives of about 1.3 hours and 9 hours, respectively. About two thirds of the administered drug is excreted unchanged in the urine, probably by glomerular filtration. Approximately 50% is recovered in the urine in the 24 hours following an IV or IM injection. The rate of excretion, therefore, is highly influenced by renal function; concentrations in plasma are greatly elevated if usual doses are given to patients with renal impairment with only up to 20% excreted in 24 hours. Observations indicate that it is difficult to eliminate bleomycin from the body by dialysis.