Chapter 7 
reflecting the approximately 16-hour half-life of cotinine (Benowitz et al., 
1983a). Because of the relatively small circadian variation, cotinine levels 
can be measured at various times of the day, and this value can be used as 
representative of the average daily cotinine level. 
It is possible, by measuring all the metabolites in the urine, to account 
for an average of 90 percent of the nicotine dose (Benowitz et al., 1994). 
An approach to estimating nicotine consumption is to measure all the 
metabolites in the urine and sum them up. At steady state (where the rates 
of intake of drug and generation of metabolism are the same as rates of 
elimination of drug and metabolites), this sum of all metabolites in a 
24-hour urine excretion reflects the amount of nicotine that a person takes 
in each day. 
NICOTINE CONTENT As noted earlier, cigarette content is not the same as cigarette 
OF TOBACCO VS. yield or delivery. Figure 2 shows data from a 1983 study 
FTC YIELD (Benowitz et al., 1983b) that investigated the nicotine content 
of tobacco. The nicotine concentration of tobacco averaged 1.6 percent. 
There was no relationship between nicotine content in the whole tobacco 
rod and the FTC-predicted nicotine yield. There was a significant inverse 
relationship between the concentration of nicotine and the FTC nicotine 
yield. Thus, the yield as measured by smoking machine gives no information 
whatsoever about the content of nicotine or other potential toxins in the 
tobacco. The content of nicotine in the tobacco simply represents the 
ultimate limit of the nicotine dose. The FTC method provides no information 
about the amount of nicotine that could be obtained from the tobacco if 
a person smoked it in a way to optimize intake. 
QUANTITATING There are four general methods for quantitating the intake of 
NICOTINE INTAKE nicotine from tobacco: (1) In circadian fashion, measure blood 
IN SMOKERS nicotine levels during cigarette smoking (Benowitz and Jacob, 
1984a and 1984b). If the clearance of nicotine also is measured by 
intravenous infusion of nicotine, blood levels during smoking can be 
converted to an absolute daily dose of nicotine. (2) The same can be done 
with blood level data after a person has smoked one or two cigarettes 
(Benowitz et al., 1991). (3) Blood cotinine levels during ad libitum cigarette 
smoking have been used widely to estimate nicotine intake, which is 
discussed below. (4) Finally, as mentioned by Byrd and colleagues (1995), 
measuring urine nicotine and metabolites during ad libitum smoking can be 
used to estimate nicotine intake. These four ways can be used to address the 
question of how much nicotine is being taken into the body from smoking. 
Table 1 presents a summary of data on the dose per cigarette from 
the first three methods. The first method was used to study 44 smokers, 
measuring blood levels during 24 hours of smoking, at steady state (Benowitz 
and Jacob, 1984a, 1984b, and 1985). The dose was estimated to be about 
1 mg per cigarette, with a range of 0.37 to 1.60 mg per cigarette. 
95 
