In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest.

This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups.

No abstract

Subjective responses, including those associated with abuse liability and changes in frontal electroencephalographic activity, were assessed in abstinent alcoholic men and control subjects after administration of alprazolam, diazepam, buspirone, and placebo. Plasma concentrations of alprazolam, diazepam, and desmethyldiazepam also were determined. Abuse liability scales were elevated for alcoholic participants above control levels after alprazolam and diazepam. Areas under the concentration-time curve differed only for desmethyldiazepam, which was lower for the alcoholic participants. Compared with control subjects, alcoholic participants had greater declines in the absolute power of the alpha band after diazepam challenge. Alcoholic participants, unlike control subjects, had areas under the effect-time curve for alpha and theta bands that were lower after administration of alprazolam or diazepam than they were after receiving placebo. These results suggest that alprazolam and diazepam are more likely to be abused by alcoholic men than by nonalcoholic men and that alcoholic men have enhanced sensitivity to the effects of benzodiazepines on alpha and theta activity.