Our data support the hypothesis that a drug’s kinetics partially determine drug abuse. At least two kinetic characteristics, when present together (rapid absorption and intermediate half-life) were associated with higher abuse of benzodiazepines. It is not surprising that absorption seems to play a more important role than lipophilicity in determining abuse potential since time to enter the systemic circulation is in the order of several minutes to hours for most benzodiazepines while time to enter the brain is only in the order of a few minutes at most . Thus, absorption of the drug is the rate-limiting step. It is interesting, however, to speculate on the influence ofmicrokinetics at the receptor level on the abuse liability ofthe benzodiazepines. Asynchrony between plasma concentrations and receptor effects has been described for several drugs . Certainly a better understanding of benzodiazepine microkineti cs at the recept or level would enable a more refined testing of the hypothesis that the rapid availability of the drug at the receptor level, rather than rapid absorption, is the factor that provides the optimal condition to encourage drug self-administration. buy flovent inhaler
The dose ofthe benzodiazepine is another factor influencing abuse. This is not surprising since previous animal and human studies have shown clearly that ‘drug-liking’ is directly related to the dose ofbenzodiazepine administered .
The improved understanding of the role of kinetics in abuse potential may help to prevent and treat abuse. Since rapid absorption seems to be associated with higher abuse liability, factors to decrease the rate of absorption should decrease the
Figure 2) Relative abuse of different benzodiazepines adj usted for overall use and market years. Numbers show ratio of the observed abuse (expressed as a percentage of total abuse) to expected abuse (based on usage data adjusted by number of years on the market and expressed as a percentage of total use)
Figure 3) Correlation of composite score of kinetic variables and dose with observed abuse of benzodiazepines abuse liability of drugs that are pharmacologically reinforcing.