Figure 8.

Simulations of nicotine pharmacokinetics and pharmacodynamics during smoking. (A) The pharmacokinetic/pharmacodynamic model, implemented in Matlab SimBiology. Individual parameters and structures and smoking dosages are presented in Table S2 and in Supplemental ZIP File. (B1) Nicotine concentrations in the plasma/CSF/ER and in the “sequestered” compartment, during 40 simulated hours for the standard habit (Table S2 and Supplemental ZIP File). The latter compartment was termed the “peripheral compartment” by Benowitz et al. (1991), but that terminology is less preferable in discussions of the nervous system. Note the logarithmic [nicotine] scale. (B2) Effects on the two processes shown in A. Note that the standard habit nearly activates nAChR protein chaperoning (inside-out process) >50%, but activates nAChR channel activation (outside-in process) <20%.