Pharmacokinetics and bioavailability of etintidine in beagle dogs: Effects of routes of administration,doses, dosage forms,and chronic dosing

Etintidine HCl is an H₂ receptor antagonist which has been under clinical trial for the treatment of duodenal ulcer diseases. Our studies are to determine the effects of routes of administration, doses, dosage forms, and chronic dosing on the bioavailability and pharmacokinetics of etintidine (E) in the beagle dog. Salient findings are:

• 1 Plasma levels of etintidine after i.v. administration of 200mg of E followed a 3-exponential decay with a terminal t_½ of 1.7 h.
• 2 Following oral administration of 200mg of E in capsules, tablets, or a solution dosage form to dogs, etintidine was rapidly and nearly completely absorbed with no significant first-pass elimination.
• 3 A proportional increase in the amount of etintidine absorbed in the dogs occurred as the administered doses increased from 30 to 180 mg kg^?1 and this relationship did not change with repeated dosing.
• 4 Some accumulation of etintidine took place during the 52 weeks of chronic dosing.