Absorption 

Bleomycin is well absorbed in animals upon parenteral administration. Intramuscular injection of 15 units in humans resulted in a maximum serum concentration of 1 mU/mL 30 minutes after administration. Intravenous injection of 15 units in humans resulted in a maximum serum 

concentration of 3.3 mU/mL. 

Distribution 

In mice, bleomycin diffusing from the blood produces high concentrations in the skin, lungs, kidneys, peritoneum, lymphatic system and susceptible tumour tissue if present. Bleomycin crosses the placenta, but does not cross the blood brain barrier. Equilibrium dialysis and gel permeation experiments suggest that less than 1.0% of the drug is protein bound after incubation with normal human serum in vitro. 

Metabolism 

The majority of a bleomycin dose is not readily metabolised. The highest rate of metabolism occurs in the liver and gastrointestinal tract. A lower rate of metabolism also occurs in skin, lungs, kidneys, muscle and serum. The products of bleomycin metabolism are not known.

Excretion 

Bleomycin is primarily excreted in the urine. After intravenous injection an average of 40% of the administered dose is recovered unchanged in the urine within 24 hours. After intramuscular injection 20% is recovered in the urine after six hours. The plasma half-lives have varied from 15 to 60 minutes in patients with normal renal function following intravenous administration. The serum half-life is prolonged in patients with renal dysfunction. In one patient with severe renal dysfunction the biological half-life was 21 hours when the creatinine clearance was 10.7 mL/minute, and 13 hours when the creatinine clearance was 15.2 mL/minute. There were undetectable serum levels of bleomycin 72 hours after the intravenous dose.

Interactions with other medicines 

-Pharmacodynamic interactions 

Anaesthetics, general and oxygen. Use in patients previously treated with bleomycin may result in rapid pulmonary deterioration, since bleomycin causes sensitisation of lung tissue to oxygen. 

Radiation therapy. Radiation therapy, especially to the chest area, either prior to, during or after bleomycin therapy may result in increased bleomycin toxicity. Dosage adjustment may be necessary. 

Antineoplastic agents. Concurrent use may result in increased bleomycin toxicity, or in occurrence of pulmonary toxicity at lower doses of bleomycin (see Precautions).

Combination therapy. Pulmonary toxicity may be observed at lower doses of bleomycin when bleomycin is administered as part of a multidrug treatment regimen. Patients should be closely monitored for signs of pulmonary toxicity (see Precautions). 

Granulocyte colony stimulating factor. It has been suggested that concomitant administration of G-CSF and bleomycin may increase the risk of bleomycin induced pulmonary toxicity, especially at higher doses, although this has not been confirmed in clinical trials. If G-CSF is added to bleomycin containing treatment regimens, patients should be closely observed for signs of pulmonary toxicity (see Precautions). 

-Pharmacokinetic interactions 

Cisplatin. Cisplatin induced renal function impairment may result in delayed clearance and bleomycin toxicity even at low doses. An increased incidence of bleomycin induced pulmonary toxicity has been observed when these two agents are administered as part of an antineoplastic treatment regimen. Dosage reduction may be required (see Precautions). 

Digoxin. Serum levels of digoxin may be reduced and its actions may be decreased. It is thought that drug induced alterations of the intestinal mucosa may be involved in the reduced gastrointestinal absorption. 

Phenytoin. Serum concentrations of phenytoin may be decreased due to decreased absorption or increased metabolism of phenytoin.