Delayed absorption of phenylbutazone caused by desmethylimipramine in humans

The effect of DMI on the absorption of orally administered phenylutazone was studied in human subjects. A single pretreatment with 50 mg of DMI delayed the time to peak absorption of phenylbutazone in 4 volunteer subjects. Peak phenylbutazone plasma levels in untreated subjects were reached 2-6 hr after oral phenylbutazone administration while peaks were not attained even 10 hr after DMI treatment. A seven-day chronic pretreatment with DMI (25 mg, 3 X day) delayed time to peak absorption of phenylbutazone in 4 chronically depressed females from 2 hr (before DMI) to 4-10 hr when phenylbutazone was administered 30 min after the last dose of DMI. When phenylbutazone was given 14 hr after the last dose of a ten-day chronic treatment with DMI (25 mg, 3 X day) to another group of 4 females, no clear effect on the time to peak absorption was observed although plasma levels of phenylbutazone were lower in all 4 patients. The individual differences in phenylbutazone plasma levels may be due to individual variations in the metabolism of DMI.