title: Pharmacokinetics and bioavailability of intravenous and intramuscular lorazepam with an adjunct test of the inattention effect in humans.
abstract: Single dose pharmacokinetics and bioavailability of intravenous and intramuscular lorazepam were investigated in 6 younger healthy human volunteers of either sex. The plasma concentration profile after intravenously administered lorazepam could in all cases be fitted by NONLIN to a biexponential function of time with a mean terminal (biological) half-life of 14.10 hrs +/- 2.94 S.D. (range 9.68 - 18.42 hrs). The mean half-life of the initial alpha-phase of distribution was 0.31 hrs +/- 0.11 S.D. The mean apparent volume of distribution derived from AUC, Vd-area (=Vd beta), was 1.24 1 kg-1 +/- 0.17 S.D. Mean plasma clearance of the drug was 62.17 ml kg-1 hr-1 +/- 8.85 S.D. The apparent central volume of distribution characterizing the open two-compartment pharmacokinetic model was 0.59 1 kg-1 +/- 0.19 S.D. After intramuscular administration to the same subjects the plasma concentration time lapse could be described by either tri- or bi-exponential kinetics, which are representative of open two- and one-compartment models with absorption phases, respectively. Mean biological half-life was 14.01 hrs +/- 2.31 S.D. and Vd-area 1.24 l kg-1 +/- 0.14 S.D., both values in full agreement with the findings based on intravenous administration. Half-life of the absorption phase varied from 0.08 to 1.76 hrs. Mean systemic availability of the drug was 88.8% +/- 8.3 S.D. The inattention effect of lorazepam was assessed by exposing the subjects during the intravenous pharmacokinetic experiments to a binaural stimulation test, which revealed various degrees of acute reduced attention in only three of the subjects.
mesh_terms: D000328:Adult; D000647:Amnesia / Q000139:chemically induced; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001288:Attention / Q000187:drug effects*; D001682:Biological Availability; D005260:Female; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007700:Kinetics; D008140:Lorazepam / Q000378:metabolism* / Q000494:pharmacology; D008297:Male
chemical_list: D014151:Anti-Anxiety Agents; D008140:Lorazepam