THE PHARMACOKINETICS AND HEMODYNAMIC-EFFECTS OF INTRAVENOUS AND INTRAMUSCULAR DEXMEDETOMIDINE HYDROCHLORIDE IN ADULT HUMAN VOLUNTEERS

Background. Dexmedetomidine is an alpha2 agonist with potential utilit y in clinical anesthesia for both its sedative and sympatholytic prope rties. Methods. The pharmacokinetics and hemodynamic changes that occu rred in ten healthy male volunteers were determined after administrati on of dexmedetomidine 2 mug/kg by intravenous or intramuscular route i n separate study sessions. Results. The intramuscular absorption profi le of dexmedetomidine, as determined by deconvolution of the observed concentrations against the unit disposition function derived from the intravenous data, was biphasic. The percentage bio-availability of dex medetomidine administered intramuscularly compared with the same dose administered intravenously was 73 +/- 11% (mean +/- SD). After intramu scular administration, the mean time to peak concentration was 12 min (range 2-60 min) and the mean peak concentration was 0.81 +/- 0.27 ng/ ml. After intravenous administration of dexmedetomidine, there were bi phasic changes in blood pressure. During the 5-min intravenous infusio n of 2 mug/kg dexmedetomidine, the mean arterial pressure (MAP) increa sed by 22% and heart rate (HR) declined by 27% from baseline values. O ver the 4 h after the infusion, MAP declined by 20% from baseline and HR rose to 5% below baseline values. The hemodynamic profile did not s how acute alterations after intramuscular administration. During the 4 h after intramuscular administration, MAP declined by 20% and HR decl ined by 10%. Conclusions. The intramuscular administration of dexmedet omidine avoids the acute hemodynamic changes seen with intravenous adm inistration, but results in similar hemodynamic alterations within 4 h .