Pharmacokinetics of flunitrazepam in rats studied by a radioreceptor assay

In rat the kinetics of flunitrazepam (FNZ) was evaluated by a radioreceptor assay (RRA) after i.v. administration of 1 mg/kg and after oral administration of 1 and 3 mg/kg. The i.v. kinetics is biexponential and the g.i. absorption is very rapid (with a plasma peak at 0.25 hour) with a good bioavailability (69%); the apparent distribution volume is high, 4.8 L/kg; the half-life is equal to 3.5 hours; the elimination constant is equal to 0.8 h-1; the urinary excretion of FNZ-equivalent is negligible; the plasma total clearance is equal to 3.9 (L/kg)h-1. The concentrations of FNZ-equivalents after oral administration of 1 mg/kg show a peak at the 2-nd hour with a very high concentration in the following organs (in decreasing order): brain, kidneys, heart, liver; after 8 hours no FNZ-equivalents are present in these organs except in the brain, which shows detectable concentrations at the 32-nd hour. The peak concentrations of FNZ-equivalent in brain, kidneys and heart are higher than the corresponding peak concentration in plasma.