[Preclinical pharmacologic evaluation of bleomycin A6].
Bleomycin A6 is an antineoplastic antibiotic. Toxicologic study showed that the LD50 values of bleomycin A6 in mice were 92 +/- 7.4 mg/kg (IV), 72 +/- 5.6 mg/kg (IM), 82 +/- 4.5 mg/kg (SC), 102 +/- 0.6 mg/kg (IP) and 520 +/- 0.1 mg/kg (PO), respectively. Wistar rats were divided into 6 groups. Doses of 20, 10, 5, 2 and 0.5 mg/kg/day were given intraperitoneally every other day for 60 days. Renal damage to various degrees was found in rats with doses higher than 2 mg/kg. However, no pathologic changes were observed in the liver, heart, lungs, spleen, stomach, intestines, pancreas or brain. Three groups of dogs (3 in each group) were injected i.v. every other day for 60 days with a dose of 1.0, 0.5 and 0.1 mg/kg, respectively. The three dogs receiving 1.0 mg/kg died between the 4th and 7th week. Dogs treated with 1.0 and 0.5 mg/kg had renal damage and skin ulceration. With a dose of 0.1 mg/kg, dogs showed good tolerance and no renal damage was found. Multiple doses of bleomycin A6 injected into rabbit muscles caused no obvious local changes. After IV injection into rabbits, the maximal serum concentration of bleomycin A6 was 18.5 micrograms/ml, having a half life of 2.8 hours and 7.7% of the drug were excreted in the urine within 12 hours.
Lin
F T
FT
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D001761:Bleomycin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity / Q000031:analogs & derivatives; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D007668:Kidney / Q000187:drug effects*; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000903:Antibiotics, Antineoplastic; C052656:bleomycin A6; D001761:Bleomycin