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Bioavailability from various galenic formulations of flunitrazepam.

The absolute and relative bioavailability of flunitrazepam (Rohypnol) tablet, oral solution and suppository formulations was determined in a cross-over study on 6 healthy volunteers. The tablet and the oral solution were shown to be bioequivalent, absorption being at least 80%. For flunitrazepam suppositories the bioavailability was found to be about 50%. The plasma concentrations are described on the basis of a three-compartment model, the adjustment of the curves from the same subject being made simultaneously. The central compartment and the second compartment are about equal in size and rapid exchange takes place between them. The third compartment is about four times as large as the central one. The slow reflux of the compound from the third to the first compartment is the rate determining factor for the overall elimination in the beta-phase.