EFFECT OF DESIPRAMINE ON INTESTINAL ABSORPTION OF PHENYLBUTAZONE AND OTHER DRUGS

Peak plasma phenylbutazone levels were reached 1-2 hr after the oral administration of phenylbutazone (40 mg/kg) to rats. Pretreatment with desipramine (DMI, 15 mg/kg) 1 hr before the oral administration of phenylbutazone resulted in a marked decrease in plasma phenylbutazone levels. Phenylbutazone and oxyphenylbutazone levels in 24 hr urine samples of DMI pretreated animals were lower than in controls. The stomach of DMI pretreated rats contained about 4 times more phenylbutazone than controls 4 hr after the oral administration of phenylbutazone while the values were similar after 14 hr. Intestinal contents of phenylbutazone were about 4 times higher in DMI pretreated animals even 14 hr after the oral administration of phenylbutazone. Pretreatment with DMI had no effect on the plasma levels of orally administered amphetamine (15 mg/kg) or pentobarbital (30 mg/kg) while plasma levels of orally administered oxyphenylbutazone (15 mg/kg), hydrocortisone (50 mg/kg) and salicylate (200 mg/kg) were lowered. The possibility that DMI inhibits the absorption of some orally administered drugs by relaxing gastro-intestinal smooth muscle is discussed. © 1969.