A different picture of relative benzodiazepine abuse emerges when abuse data are adjusted for total market exposure and compared with expected abuse (Figure 2). A ratio of observed abuse to expected abuse of 1:1 indicates that proportion of abuse parallels proportion of use. Some benzodiazepines, such as diazepam, have ratios much higher than 1:1, while others have ratios much lower (eg, flurazepam). These data suggest that there is differential abuse of benzodiazepines and factors other than availability play a role in determining which benzodiazepines are preferred.
Kinetic variables, dose and observed abuse: The kinetic variables described in the ‘Data Analysis’ section (absorption rate, lipophilicity, plasma elimination half-life) and maximum prescribed dose (relative to receptor affinity) were correlated with the observed abuse ratio to determine if any single kinetic factor could predict abuse and dependence potential. The only significant relationship was between elimination rate rank and abuse rank (r=0.71, P=0.02). No other significant relationships were observed (Pearson correlation coefficients: dose rank versus abuse rank: r=0.44, P=0.2; absorption rate rank versus abuse rank: r=0.43, P=0.2; lipophilicity rank versus abuse rank: r=0.15, P=0.6). ventolin inhaler
However, Kendall’s coefficient of concordance indicated agreement among the rankings of observed abuse, absorption rate, dose and elimination half-life (W=0.50, degrees of freedom [df]=9,P=0.03). In addition, a composite score combining the ranks of absorption rate (rapid), dose (high) and elimination half-life (intermediate) correlated with observed abuse rank (r=0.80, P=0.005), suggesting that more rapid absorption, higher dose and intermediate half-life contribute to abuse potential (Figure 3).