Quinine and quinidine inhibition of pentobarbital metabolism

Abstract

The influence of quinine hydrochloride pretreatment on pentobarbital metabolism was assessed by measurements of sleeping times, ld 50 values, hepatic microsomal metabolism and relative rates of decay of plasma levels of pentobarbital. These studies were conducted in Swiss-Webster mice, Sprague-Dawley rats and Angora or Toggenburg goats. Quinine increased sleeping time in phenobarbitalstimulated and unstimulated mice and in rats, decreased the ld 50 of pentobarbital in mice, and increased the plasma half-life of pentobarbital in goats. Quinine in various concentrations inhibited the hepatic metabolism of pentobarbital in 9000 g supernatant incubation mixtures ( K I = 2.9 × 10 −5 M), as did quinidine ( K I = 7.6 × 10 −6 M). Duration of barbital hypnosis was not affected by quinine pretreatment. The presence of quinine in plasma decreased the extent of protein binding of pentobarbital m plasma from humans, ponies, swine, goats and mice. The pentobarbital concentration in brains from quinine-pretreated mice was not significantly different from the concentration in brains from control animals at awakening. The results obtained from these experiments indicate that quinine and quinidine alter the duration of action of pentobarbital by inhibition of microsomal enzymes.