782 



318 GORi AND LYNCH 



Piasma 

 NIcotina 



1 I 



I 111 I 



I I I 1 I II 



I I < tl4« 1 It 



I iitt »<3 a I II I 



I B S7 a S»«21t II II 1 



) I > >i I I JIM t limit I 11 II 



a III 1 >4 4 «3 313 VtuJII 

 21*1 I <1M2<3 I1U«I W. 



FTC Nkxifno (mg/cltf 



Fig. 2. IndividuaJ plasma nicotine values as a function of FTC nicotine yield of cigarettes smoked. The 

 digit in each data point irdicatcs the numoer of individual obscrvaiiotu in the domain of that point • 

 mdicaies 10 or more observations. The significance o( r a P < 0.001. 



bioavailability per cigarette. Published information on nicotine disposition in man (5, 

 6) estimates mean plasma nicotine half-life h = \20 min, and mean volume of dis- 

 tribution y^ = 2600 ml/kg. For each individual, the weight W^is known, and dt = 900 

 min/(CPD - 1) is the average interval between cigarettes smoked. Each individual 

 was sampled in late afternoon, 10 min after smoking a cigarette, giving plasma nicotine 

 values at or near peak steady-state /^Nic)s.s. On this basis, individual mean nicotine 

 intake per cigarette I-MNIC can be estimated as 



I-MNIC = /'(Nic)s.s. . ^f' • V^*[\ - (0.5)*/*] 



Because V^ and h are estimated population means, the I-MNlC values cannot be 

 interpreted as precise individual estimates, but the statistical aggregate of their values 

 is reasonably representative of sample trends. 



This conclusion is even more justified since published data (5) do not show corre- 

 lation between half-life and dose, volume of distribution and dose, half-life and volume 

 of distribution, or half-life and plasma levels. Independent direct measure of mean 

 nicotine intake in smokers has produced data consistent with the mean estimates of 

 our study (9). Mean values of estimated ."-.icotine intakes are reported in Fig. 4, which 

 also shows the mean trend of daily nicotine intake per kilogram of body weight, given 

 here for its pharmacodynamic significance. In this regard it should be noted that in 

 our sample the distribution of body weights was associated with less than 1% of the 

 variation in the FTC nicotine yield of the cigarettes smoked (K = 66.2 h- 3.76Ar; r 

 = 0.09, .«>< 001). 



Sicoiine-Cotinine Relationship 



Previous studies have shown a good correlation of plasma nicotine and cotinine (r 

 = 0.84). after accurate selection of subjects, and blood samplmg limed to synchronize 

 pharmacokinetic variables near steady-state values ( 19, 20). Recently, Benowitz et al. 

 (8) and Lynch (29) reported kinetic parameters for cotinine disposition in man. showing 

 no correlation between dose and half-life, nor between plasma levels and half-life. 



