EFFECT OF GRADUATED INTRAVENOUS AND STANDARD RECTAL DOSES OF INDOMETHACIN ON CEREBRAL BLOOD-FLOW IN HEALTHY-VOLUNTEERS

Administration of indomethacin may aid treatment of intracranial hyper tension, and the present study was conducted to determine the optimal dose, In healthy volunteers, cerebral blood flow (CBF) has been shown to decrease considerably after a bolus dose of indomethacin, 0.4 mg/kg , followed by continuous infusion, 0.4 mg/kg/h. This decrease was sust ained for 6 h without any evidence of adaptation. In a randomized stud y in healthy volunteers, indomethacin, 0.1, 0.2, and 0.3 mg/kg, was gi ven as bolus, followed by continuous infusion of 0.1, 0.2, and 0.3 mg/ kg/h. CBF decreased from normal levels (52-74 ml/100 mg/min) to 38-51 ml/100 g/min. There were no differences among the three groups in CBF reduction, and the reduction was sustained during the 6-h infusion per iod. Rectal application of 100 mg indomethacin was found to reduce CBF from normal levels (54-74 ml/100 mg/min) to 33-48 ml/100 mg/min. Thes e low levels were only sustained for 2 h, and values returned to norma l over the next 6 h. We observed no rebound phenomenon 2 h after stopp ing the infusion and no rebound after 100 mg of rectally applied indom ethacin. Since a dose as low as 0.1 mg/kg/h is effective, it is possib le to treat most patients in a 24-h schedule without going over maximu m recommended doses.