Abuse liability design

Foltin, R. W., The importance of drug self-administration studies in the analysis of abuse liability An analysis of caffeine, nicotine, anabolic steroids, and designer drugs. Annual Meeting of the American Academy of Psychiatrists in Alcoholism and Addictions (1990, Santa Monica, California). American Journal on Addictions Spr Vol 1(2), 139-149, 1992. 

The toxicity of abused substances is considered because misuse has the potential to create public-health problems and because the presence or absence of toxic effects can limit abuse liability. Toxicity data can be obtained in studies designed specifically for that purpose as well as from studies of other pharmacological effects such as those listed above. 

Because faster onset of action is associated with higher potential for abuse, abuse-liability assessment should include consideration of whether a formulation can be altered to increase the speed of onset. There are numerous examples of abuse of a medication by a route other than that intended by the manufacturer. The sustained-release oral form of oxycodone, designed to deliver an initial rapid dose followed by slow release, has been widely abused by chewing the tablet, thus releasing the entire content of the tablet at once.65 There is also evidence for intravenous use of sublingual buprenorphine tablets.66 Transdermal systems developed to deliver medication slowly for extended periods of time have been prime targets for misuse,67 as discussed below in the case study of fentanyl. 

Comments. The clearest lesson from the butorphanol experience is that when a drug is introduced to a new population, it is important to determine whether extant abuse-liability studies will generalize to that population. If not, then clinical trials should be designed to detect signs of abuse in that population, and careful postmarketing surveillance should occur. The goal is not to prevent patient access to necessary medications, but to ensure that providers and patients have adequate information about the risks of such medications. 

Comments. The clearest lesson from the DXM experience is that when designing an abuse-liability study, it is important to consider all possible effects that can make a drug abusable, bearing in mind that effects to which a particular study sample is insensitive or averse may be desired effects in others. 

The preclinical data can also impact the design and breadth of the clinical abuse liability package that will be expected. In addition, the data from the dependence... 

A manufacturer must allow for foreseeable abuses and misapplication of a product. To reduce liability associated with misuse, a designer can provide warnings and instructions that address foreseeable misuses. 

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