Analytical and biological inequivalence of two commercial formulations of the antitumor agent bleomycin.
Bleomycin is an antitumor agent which is a mixture of glycopeptides containing at least 55-75% bleomycin A2 and 25-32% bleomycin B2 fractional composition. Two bleomycin formulations, bleomycin sulfate, USP (Blenoxane, Bristol-Myers Squibb Oncology, Princeton, N.J.) and bleomycin HCI (Tianjin Hebei Pharmaceutical, Tianjin, China) were compared analytically and biologically. Reverse-phase high-performance liquid chromatography (HPLC) analyses using the USP methodology showed that Blenoxane contained primarily (69%) bleomycin A2 and 29.3% bleomycin B2. In contrast, Tianjin-supplied bleomycin HCI contained 97% bleomycin A5 fraction. In vitro tumor cell growth inhibition assays showed equivalent activity in human OVCAR-3 ovarian cancer cells and slightly greater potency in murine L-1210 leukemia cells for the Tianjin formulation. In C57/B1 mice bearing B-16 melanoma tumors, Tianjin-supplied bleomycin produced slightly greater tumor growth inhibition at the expense of greater drug-induced lethality at higher dose levels. These studies show there are significant differences in two international bleomycin formulations. These compositional differences lead to altered biologic effects.
Dorr
R T
RT
Pharmacology Department, College of Medicine, The University of Arizona, Tucson 58724, USA.
Meyers
R
R
Snead
K
K
Liddil
J D
JD
D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D001761:Bleomycin / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D013810:Therapeutic Equivalency; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin