The effect of colchicine-specific active immunization on colchicine toxicity and disposition in the rabbit.
Anti-colchicine antibodies raised in rabbits are effective at protecting rabbits from acute colchicine intoxication. The positive effect depends on the ratio between the binding site capacity of the specific antibodies and the colchicine dose. Immunized rabbits receiving 6 mg/kg colchicine intravenously (LD100) died within 8 h as rapidly as those of the non-immunized control group. In contrast, if the colchicine dose was reduced to 3 mg/kg (LD83), rabbits were protected and mortality decreased to 17%. Study of plasma colchicine pharmacokinetics indicated that colchicine was totally sequestrated by antibodies in the 3 mg/kg group and only 55-80% sequestrated in 6 mg/kg group. This sequestration contributed to reducing colchicine diffusion into tissues (the volume of distribution decreased 7-fold) and to increasing the terminal half-life and the total body clearance of the drug. Moreover, as the slope of the dose-lethality curve was steep, a small binding capacity was sufficient to neutralize colchicine toxicity at 3 mg/kg. Results clearly indicate that anti-colchicine antibodies are able to effectively sequestrate colchicine. Moreover, the amount of circulating antibodies is a crucial limiting factor for the effectiveness of immunotoxicotherapy.
Scherrmann
J M
JM
Inserm unité 26, Hôpital Fernand Widal, Paris, France.
Urtizberea
M
M
Pierson
P
P
Terrien
N
N
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage* / Q000276:immunology; D000937:Antigen-Antibody Reactions; D001666:Binding Sites, Antibody; D003078:Colchicine / Q000276:immunology / Q000493:pharmacokinetics / Q000633:toxicity*; D006207:Half-Life; D007114:Immunization; D011041:Poisoning / Q000517:prevention & control; D011817:Rabbits; D051381:Rats
D000906:Antibodies; D003078:Colchicine