The pharmacokinetics of bleomycin in man.

Of all the bleomycin-containing radiopharmaceuticals, bleomycin 57Co has proven the most useful whole-body tumor-imaging agent. We have studied its in vitro physicochemical properties and in vivo disposition in animals and man to optimize its use as a scanning agent. High-pressure liquid chromatographic analysis of the standard bleomycin 57Co preparation (1 unit bleomycin plus 1 mCi chloride 57Co showed it to contain 1% free chloride 57Co). Dialysis experiments showed that bleomycin 57Co does not dissociate as it diffuses through a dialysis membrane. In nine patients, bleomycin 57Co had a t 1 2/β of 3.4 h, a t 1 2/γ of 45.8 h, a Vd of 12.1 liters/m2 and a 24-h urinary excretion of 82.1% of the administered dose. In comparison, bleomycin, assayed by radioimmunoassay, had a terminal phase plasma t1/2 of only 4.0 h, a similar Vd (17.3 liters/m2), and a 24-h urinary excretion of only 44.8%. Bleomycin 57Co tumorto-plasma concentration ratios ranged from 14.1–23.8 at 1 day to 5.4 at 2 days after administration. Our finding that tumor imaging with bleomycin 57Co is best achieved at 24 h is well explained by its almost complete urinary elimination in the first few hours after administration and the peak tumor-to-plasma ratio achieved at 24 h. One disadvantage of bleomycin 57Co as a scanning agent is its very extended plasma t1/2 In rabbits chloride 57Co has the same prolonged plasma terminal elimination phase (t 1 2/γ ) as our standard bleomycin 57Co preparation, which contains chloride 57Co as a 1% impurity. Removal of this impurity prior to scanning or use of cold cobalt chloride to help eliminate it from the plasma might result in a shortened bleomycin 57Co plasma t 1 2/γ .