Fab-bound Colchicine Appears to Adopt Fab Fragment Disposition in Rats

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Abstract
The disposition of colchicine-specific Fab fragments and the effect of Fab fragment administration on the disposition of colchicine were studied in anaesthetized bile duct-cannulated rats. One group of rats (n = 6) received a 125I-Fab dose of 38 mg kg−1 i.v. The plasma disposition was characterized by a volume of distribution of 179 ± 48 mL kg−1, total body clearance of 1·02 ±0·07 mL min−1 kg−1, t½α of 0·17 ± 0·03 h and t½α of 1·3 ± 0·3 h. Fab fragments were in part excreted by the renal route (15·6 ± 6% of the Fab dose), while biliary excretion was a minor route (< 2% of the Fab dose). Two other groups of rats received 15 μg kg−1 colchicine (n = 6) or 15 μg kg−1 colchicine plus 38 mg kg−1 colchicine-specific Fab fragments (n = 6) by intravenous infusion. Pharmacokinetics of colchicine was markedly altered in the Fab-colchicine-treated rats. In this group, distribution volume and total body clearance of colchicine were decreased by factors of 22 and 10, respectively, compared with the values in the colchicine-treated group and were very similar to those of Fab fragments. An 80% reduction of cumulative biliary excretion of colchicine was observed in Fab-colchicine-treated rats (P < 0·01). The fraction of colchicine dose excreted by the urinary route was 38 ± 6·9 and 9 ± 0·7% respectively in Fab-colchicine- and colchicine-treated groups (P < 0·01). These data show that during Fab treatment, colchicine followed the elimination kinetics of Fab fragments. This study supports the view that Fab fragments could be of benefit in acute colchicine poisoning by neutralizing colchicine in the vascular compartment and imposing its elimination kinetics on colchicine.

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