Absorption, excretion and metabolism of tiquizium bromide in dogs, and relationship between pharmacological effect and plasma levels of unchanged drug

Abstract

1. The disposition of ¹⁴C-tiquizium bromide was investigated in dogs after oral administration and i.v. administration.

2. After oral administration, max. blood concn. of radioactivity were obtained from one to three hours after dosing. The half-lives of the terminal phase were 7.1 h (i.v.) and 9.4-12.0 h (p.o.). The relative bioavailability was 26%. The urinary excretion in three days was 24% (i.v.) and 5-9% (p.o.).

3. The most important mechanism of biotransformation was hydroxylation in the 5-position of the thiophene ring, and glucuronides of the isomeric hydroxylated products of tiquizium bromide were found in urine.

4. The time-course of the inhibitory effect of tiquizium bromide on stomach contraction correlated well with the plasma levels of unchanged drug after intraduodenal administration.