The pharmacokinetics of Casodex in laboratory animals.
1. The pharmacokinetics of Casodex, a novel, non-steroidal antiandrogen, have been investigated following single oral and i.v. doses and during daily oral dosing to male and female rats and male dogs. 2. The binding of 14C-Casodex to rat, dog and human plasma proteins, determined by equilibrium dialysis, was high with values greater than 95%; in dog there was evidence for decreased binding at concentrations greater than 12 micrograms/ml. 3. Casodex was slowly absorbed over prolonged periods and its bioavailability decreased with increase in dose from 72% and 88% in male and female rats respectively at 1 mg/kg to 10% and 12% at 250 mg/kg; in dog bioavailability decreased from 100% at 0.1 mg/kg to 31% at 100 mg/kg. 4. Elimination of Casodex from plasma was slow with terminal elimination half-lives of about 1 day in rat and about 6 days in dog. On daily administration to rats Casodex accumulates slightly in plasma at 10 mg/kg but not at 250 mg/kg; in dog appreciable accumulation (9-12-fold), calculated from the ratio of trough plasma concentrations at steady state to those after a single dose, was observed at 2.5 and 10 mg/kg, but at 100 mg/kg the accumulation ratio was much lower (4-fold).
Cockshott
I D
ID
ICI Pharmaceuticals, Mereside, Alderley Park, Macclesfield, Cheshire, UK.
Plummer
G F
GF
Cooper
K J
KJ
Warwick
M J
MJ
D000284:Administration, Oral; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000813:Anilides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D004285:Dogs; D005260:Female; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D009570:Nitriles; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D014105:Tosyl Compounds
D000726:Androgen Antagonists; D000813:Anilides; D001798:Blood Proteins; D009570:Nitriles; D014105:Tosyl Compounds; C053541:bicalutamide