Absorption of enprofylline from the gastrointestinal tract in healthy subjects.
Enprofylline, a new potent bronchodilator xanthine drug, was given orally as an aqueous solution to 6 healthy subjects in single doses of 2, 4 and 6 mg/kg. The two lower doses produced plasma concentrations in the range 1-4 mg/l, i.e. in the assumed "therapeutic interval" according to previous animal studies. A high 24 h urine recovery of unchanged drug, with mean values for the three dose levels ranging from 85 to 91% of the given dose, indicated good absorption and little metabolism. The dose-corrected area under the plasma concentration-time curve rose with dose as the latter was increased from 2 to 6 mg/kg. This indicates that the elimination of enprofylline is capacity-limited at high doses. Double peaks in the plasma concentration-time curves at the higher dose levels suggested intermittent and delayed gastric emptying as a possible explanation. This hypothesis was confirmed by studies in 6 other healthy subjects, who received the drug solution by three different routes; by mouth, via a catheter in the duodenum, and rectally via a catheter in the colon. The corresponding time to peak values (mean +/- SEM) were 32.5 +/- 8.7, 13.3 +/- 2.5, and 157 +/- 23 min.
D000328:Adult; D001993:Bronchodilator Agents / Q000378:metabolism*; D003692:Delayed-Action Preparations; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D014970:Xanthines / Q000008:administration & dosage / Q000378:metabolism*
D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D014970:Xanthines; C034347:enprofylline