Pharmacologic and toxicologic profile of chymopapain B (Chemolase).
The median lethal dose (LD50) of chymopapain B in mice was 82 mg/kg (22,000 units/kg) with 95% confidence limits of 75-90 mg/kg (20, 122-24, 146 units/kg) and in rats 92 (24,683 units/kg) with 95% confidence limits of 83-102 mg/kg (22,268-27, 366 units/kg). The mechanism of toxicity was hemorrhage due to destruction of the cement substance of the blood vessels. Intervertebral disc injection of chymopapain B in the rabbit at a dose level of 186 micrograms (50 units) caused chemonucleolysis in 67% of the rabbits as evidenced by partial dissolution of the nucleus pulposus. Chemonucleolysis was also noted at higher doses. No adverse affects were noted with a 20 fold increase to 3.7 mg (1000 units). A dose of 18.6 mg (5000 units)/disc caused paralysis of the hindlegs. A dose as high as 26.6 mg (7143 units) /disc caused nearly complete dissolution of the nucleus pulposus and can cause disruption of the annulus fibrosus and death. Guinea pigs receiving a sensitizing dose of 0.003 mg/kg (0.8 units/kg) chymopapain B intraperitoneally six times over two weeks were challenged with an intravenous dose of 0.03 mg (8 units)/kg. All animals exhibited marked anaphylactic signs with a resulting 50% fatality rate.
D000707:Anaphylaxis / Q000139:chemically induced; D000818:Animals; D002917:Chymopapain / Q000008:administration & dosage / Q000633:toxicity*; D010450:Endopeptidases / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D007267:Injections; D007275:Injections, Intravenous; D007403:Intervertebral Disc; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D010450:Endopeptidases; D002917:Chymopapain