The Metabolism of Rimiterol Hydrobromide at Different Intravenous Dose Levels in the Rat

Abstract

1. The metabolism of the β₂-adrenergic agent rimiterol in the rat has been studied at intravenous dose levels of 10 μg/kg, 1.0 mg/kg and 10.0 mg/kg.

2. The plasma half-lives of ¹⁴C-labelled material were 60 min at the two lower dose levels and 31 min at the highest dose level.

3. At the lower doses 3-O-methylrimiterol and 3-O-methylrimiterol glucu-ronide accounted for 31% of the urinary ¹⁴C excretion. At the highest dose no 3-O-methylrimiterol was excreted, there was a reduction in the urinary excretion of sulphates of rimiterol, and an increased excretion of unchanged rimiterol.

4. At the highest dose level there was a delay in uptake of ¹⁴C-labelled material into the liver which was attributed to the α-adrenergic actions of the drug causing splanchnic shut down.

5. These dose-related differences in rimiterol metabolism emphasize the need for conducting metabolic studies at several dose levels.