Tofenacin hydrochloride

TNO-Wu (male, 150-250 g)^[3]

10 mg/kg (labelled, i.v. study); 25 mg/kg (non-radioactive, pretreatment)

i.v.; single dose; i.p.; single dose, 30 min before labelled dose

Excreted 48.4% of administered radioactivity in bile over 5 hr after i.v. dosing in bile fistula rats.
Eliminated 42.2% of administered radioactivity via bile after i.v. dosing in normal rats, exceeding urinary elimination.
Reached maximum blood radioactivity concentration immediately, maximum liver radioactivity concentration at 10 min, and maximum bile radioactivity concentration at 15-20 min after i.v. dosing.
Exceeded liver radioactivity concentration in bile by 5 min post-dosing, with a maximum bile-to-liver concentration ratio of 7.21 at 20 min.
Showed a sharp maximum in biliary excretion of radioactivity in the second 15-min period, followed by prolonged, reduced excretion.
Had conjugated metabolites dominate biliary radioactivity even in the first 5 min post-dosing, with free tofenacin accounting for only a small fraction.
Decreased biliary excretion of radioactivity in the first hour after administration when pretreated with proadifen.
Showed no change in biliary excretion of labelled tofenacin when pretreated with non-radioactive tofenacin.

Sheffield strain (male, 250-350 g)^[4]

5 mg/kg; 10 mg/kg; 25 mg/kg

i.p.; single dose

Did not alter thiopentone anaesthesia duration at any tested dose.

Sheffield strain (male, 250-350 g)^[4]

10 mg/kg/day; 20 mg/kg/day

i.p.; daily; 5 days; 15 days

Did not alter thiopentone anaesthesia duration at any tested dose or administration duration.