The Fate of Phenglutarimide Hydrochloride in the Rat and Man

Abstract

1. In the rat, [¹⁴C]phenglutarimide HCl was completely absorbed from the gastrointestinal tract and totally excreted in the urine within 24 h after dosing. The drug was not metabolized.

2. [¹⁴C]Phenglutarimide was widely distributed throughout the body of the rat but only very low levels of radioactivity were detected in the brain. In pregnant animals the drug traversed the placenta and radioactivity was detected in the foetus and amniotic fluid in concentrations higher than or similar to those in the maternal plasma.

3. On absorption from the gastrointestinal tract, the drug was rapidly excreted into the urine and consequently tissue levels were low.

4. In man, after oral administration of non-radioactive phenglutarimide, the drug was excreted completely in the urine as the unchanged compound within 24 h after dosing.

5. In mice, phenglutarimide inhibited the peripheral but not the central actions of oxotremorine, an observation in accord with the distribution pattern of the drug in the rat.

6. Phenglutarimide inhibited the response of the isolated guinea-pig bladder to coaxial stimulation. It is suggested that sufficiently high concentrations of phenglutarimide may be reached in the bladder in vivo to inhibit the bladder reflex in man.