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

Background. Dexmedetomidine is an alpha2 agonist with potential utility in clinical anesthesia for both its sedative and sympatholytic properties. Methods. The pharmacokinetics and hemodynamic changes that occurred in ten healthy male volunteers were determined after administration of dexmedetomidine 2 mug/kg by intravenous or intramuscular route in separate study sessions. Results. The intramuscular absorption profile 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 dexmedetomidine administered intramuscularly compared with the same dose administered intravenously was 73 +/- 11% (mean +/- SD). After intramuscular 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 biphasic changes in blood pressure. During the 5-min intravenous infusion of 2 mug/kg dexmedetomidine, the mean arterial pressure (MAP) increased by 22% and heart rate (HR) declined by 27% from baseline values. Over 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 show acute alterations after intramuscular administration. During the 4 h after intramuscular administration, MAP declined by 20% and HR declined by 10%. Conclusions. The intramuscular administration of dexmedetomidine avoids the acute hemodynamic changes seen with intravenous administration, but results in similar hemodynamic alterations within 4 h.