h a primary germ cell tumor of the brain, a peak CSF level was 40% of the simultaneously-obtained plasma level and was attained in 2 hours after drug administration. The area under the Bleomycin CSF concentration x time curve was 25% of the area of the Bleomycin plasma concentration x time curve.
Distribution
Bleomycin is widely distributed throughout the body with a mean volume of distribution of 17.5 L/m2 in patients following a 15 units/m2 intravenous bolus dose. Protein binding of Bleomycin has not been studied.
Metabolism
Bleomycin is inactivated by a cytosolic cysteine proteinase enzyme, Bleomycin hydrolase. The enzyme is widely distributed in normal tissues with the exception of the skin and lungs, both targets of Bleomycin toxicity. Systemic elimination of the drug by enzymatic degradation is probably only important in patients with severely compromised renal function.
Excretion
The primary route of elimination is via the kidneys. About 65% of the administered intravenous dose is excreted in urine within 24 hours. In patients with normal renal function, plasma concentrations of Bleomycin decline biexponentially with a mean terminal half-life of 2 hours following intravenous bolus administration. Total body clearance and renal clearance averaged 51 mL/min/m2 and 23 mL/min/m2, respectively.
Following intrapleural administration to patients with normal renal function, a lower percentage of drug (40%) is recovered in the urine, as compared to that found in the urine after intravenous administration.
Special Populations
Age, Gender, and Race
The effects of age, gender, and race on the pharmacokinetics of Bleomycin have not been eva luated.
Pediatric
Children of less than 3 years of age have higher total body clearance than in adults, 71 mL/min/m2 versus 51 mL/min/m2, respectively, following intravenous bolus administration. Children of more than 8 years of age have comparable clearance as in adults.
In children with normal renal function, plasma concentrations of Bleomycin decline biexponentially as in adults. The volume of distribution and terminal half-life of Bleomycin in children appears comparable to that in adults.
Renal Insufficiency
Renal insufficiency markedly alters Bleomycin elimination. The terminal elimination half-life increases exponentially as the creatinine clearance decreases. Dosing reductions were proposed for patients with creatinine clearance values of < 50 mL/min (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).
Hepatic Insufficiency
The effect of hepatic insufficiency on the pharmacokinetics of Bleomycin has not been eva luated.
Drug Interactions
Drugs that Can Affect Renal Clearance
Because Bleomycin is eliminated predominantly through renal excretion, the administration of nephrotoxic drugs with Bleomycin may affect its renal clearance. Specifically, in one report of 2 children receiving concomitant cisplatin with Bleomycin, total body clearance of Bleomycin decreased from 39 to 18 mL/min/m2 as the cumulative dose of cisplatin exceeded 300 mg/m2. Terminal half-life of Bleomycin also increased from 4.4 to 6 hours. Fatal Bleomycin pulmonary toxicity has been reported in a patient with unrecognized cisplatin-induced oliguric renal failure.
Clinical Studies
Malignant Pleural Effusion
The safety and efficacy of Bleomycin 60 units and tetracycline (1 g) as treatment for malignant pleural effusion were eva luated in a multicenter, randomized tr |
