Chapter 8 
varies. With other drugs, compensation can be diminished when the cost 
of compensation increases. That is, if a drug becomes too costly in terms of 
expense or physical difficulty in sustaining intake, users may not compensate 
as effectively and will not administer as much of the drug as they did when 
the cost was lower (U.S. Department of Health and Human Services, 1988; 
Lemaire and Meisch, 1985; Bickel et al., 1993). Thus, if cigarettes have low 
enough nicotine contents, smokers would be expected to adjust over time 
to lower nicotine levels rather than spend the time and money necessary to 
maintain constant dose intake. Conversely, most smokers probably would 
not smoke 160 to 200 low-nicotine-content cigarettes per day to continue 
to receive the intake that they previously obtained from conventional 
cigarettes. 
Measurement of The role of dependence is assumed by the authors and the tobacco 
Smoking and industry to be important determinants of nicotine intake. Brown 
Nicotine Intake and Williamson (1983) noted 
the basic assumption is that nicotine, which is almost 
certainly the key smoke component for satisfaction, is 
fully released to the body system before exhalation takes 
place. It is essential, therefore, to quantify the change 
in chemical composition between inhaled and exhaled 
smoke under different smoking conditions. 
Cigarette dose determination is indeed complicated, and some may 
suggest that it is so complex that use of the flawed FTC method might as 
well continue simply because it has been used for nearly 30 years. However, 
such a conclusion contradicts the enormous research advances made 
over the past 30 years. This research can be used to devise a better method. 
Furthermore, the complexity of dose determination is not unique to 
cigarettes. The Food and Drug Administration (FDA) faces this issue 
routinely whenever a manufacturer submits a new drug. Unless the drug 
is injected into a vein, determination of dosing is complicated. If the drug 
is delivered by an inhaler or oral capsule, many factors must be and are 
considered so that consumers are provided with realistic estimates of what 
they will get. In particular, they are provided with information relevant to 
the maximal doses that they are likely to receive from a drug-delivering 
product. 
To provide accurate dosing information for drug delivery systems, FDA 
uses different methods as indicated by the chemical and its delivery system; 
moreover, verification of dosing estimates is accomplished in human 
bioavailability testing studies because, in the final analysis, we care about 
the dose that people receive, not the machine-derived dose. Also, if there 
are factors that produce major changes in bioavailability, such as whether 
the drug is taken with food or on an empty stomach, this can be indicated 
in the labeling. 
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