Colchicine-specific Fab fragments alter colchicine disposition in rabbits.

摘要: High-affinity goat antibodies and Fab fragments (Ka = 1.1 x 10(10) M(-1) specific to colchicine were prepared study their effect on pharmacokinetics in rabbits. First, disposition kinetics investigated four control rabbits after administration of 0.1 mg/kg i.v. Total free plasma urine assayed by radioimmunoassay. The mean elimination half-life total was 16 +/- 2.9 h. Colchicine has a large volume distribution (8.8 1.8 l/kg) low systemic clearance (114.6 3.4 ml.h-1.kg-1). Renal represented 30.7 1.9% body clearance. fraction 70% equilibrium dialysis. Second, 1.5 h injection colchicine, infused over 0.25 with colchicine-specific at half-stoichiometrically equivalent dose compared the dose. Within 15 min infusion, concentrations increased 10- 16-fold. Mean area under concentration-time curves 20-fold controls. decreased an undetectable level period 2 fragment also produced, respectively, 24- 17-fold decrease recovered significantly higher than group: 44.7 2.3 30.9 2% dose, respectively (P less .05). These data suggest that high-affinity can sequestrate extract from tissues vascular compartment subsequent excretion renal route.