Fab-bound colchicine appears to adopt Fab fragment disposition in rats.
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, t1/2 alpha of 0.17 +/- 0.03 h and t1/2 beta 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 micrograms kg-1 colchicine (n = 6) or 15 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Sabouraud
A E
AE
Institut National de la Santé et de la Recherche Médicale, Unité 26, Hôpital Fernand Widal, Paris, France.
Urtizberea
M
M
Benmoussa
K
K
Cano
N J
NJ
Scherrmann
J M
JM
D000818:Animals; D001646:Bile / Q000378:metabolism; D003078:Colchicine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006207:Half-Life; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D007140:Immunoglobulin Fab Fragments; D003078:Colchicine