Disposition pharmacokinetics of lorazepam in the rabbit

The disposition pharmacokinetics of the sedative and anxiolytic drug lorazepam were investigated in 8 rabbits in relation to intravenous bolus injection of 0.3 or 0.6 mg of the compound. Lorazepam showed distinct linear two-compartment characteristics with a mean biological half-life (t 1/2 beta) of only 73.7 min. +/- 17.3 S.D. The mean half-life of the alpha phase of distribution was 18.4 min. +/- 4.7 S.D. The mean apparent steady state volume of distribution was 1.64 1 kg-1 +/- 0.27 S.D., Vc-mean was 1.11 1 kg-1 +/- 0.24 S.D. and Vdarea 2.26 1 kg-1 +/- 0.16 S.D. The calculated apparent volume of the peripheral compartment amounted to 0.53 1 kg-1 +/- 0.28 S.D. Compared to human data the distribution of lorazepam takes place somewhat slower in an about two-times as great apparent volume of distribution, while the disposition of the compound proceeds with an about 20 times as high rate.