Disposition and metabolism of a new benzothiophene antiestrogen in rats, dogs and monkeys

Abstract

1. A new benzothiophene-derived antiestrogen (LY156758) when orally administered was well absorbed in rats and monkeys while approx. 20% was absorbed in dogs.

2. In the rat the compound was subject to first-pass hepatic metabolism which led to low levels of parent drug in the systematic circulation together with a small amount as the glucuronide conjugate.

3. In monkeys the compound occurred primarily as the glucuronide conjugate of parent drug with very little circulating free drug.

4. The systemic bioavailability of free parent drug in plasma was 39% in rats, 17% in dogs and 5% in monkeys.

5. Excretion of the drug in rats and dogs was primarily via the bile. Approx. 1% of the dose was excreted in the urine of rats and dogs after oral dosing. In rats, at least 50% of an oral dose was excreted in bile as the glucuronide conjugate of parent drug.