Toxicology Letters, 35 (1987) 53-58 Elsevier 53 TXL 01710 MATHEMATICAL MODELLING OF NICOTINE AND COTININE AS BIOLOGICAL MARKERS OF ENVIRONMENTAL TOBACCO SMOKE EXPOSURE* (Physiological pharmacokinetic models; computer simulations) SORELL L. SCHWARTZa, ROBERT T. BALLa and PHILIP WITORSCHb “Department af Pharma~a~o~, Georgetown University Schools of~edic~ne and Dentistry, Washington, DC, and bDepartment of Medicine, George Washington Llniversity, School of Medicine, Washington, DC (U.S.A.) (Received 15 September 1986) (Accepted 23 September 1986) SUMMARY Computer software developed in our laboratory (CMATRIX) was used to design a physiological phar- macokinetic model of nicotine absorption, distributjon, metabolism and excretion in man. The model accommodates inhalation of nicotine from various environments settings and physioIogica1 conditions in man. It was also used to predict pharmacokinetic behavior of cotinine arising from nicotine metabolism. Model-predicted variations in body-fluid nicotine levels confirm that nicotine is not an acceptable quantitative marker of environmental tobacco smoke (ETS) exposure. Though cotinine pro- vides a more stable pattern, predicted interindividual variation suggests the need for specific strict sam- pling and monitoring guidelines for cotinine to be a reliable quantitative marker. INTRODUCTION Epidemiological and human toxicological studies of ETS require a means for ex- posure assessment. Emphasis is currently given to nicotine and its major metabolite cotinine as biological markers of ETS exposure. These two compounds have ob- vious qualitative specificity. This study was directed at establishing criteria necessary for using nicotine or cotinine as a quantitatively reliable ETS marker. * Presented at the International Experimental Toxicology Symposium on Passive Smoking, October 23-25, 1986, Essen (F.R.G.). Abbreviation: zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA AUC, area under the curve; ETS, environmental tobacco smoke. 0378-4274/87/$03.50 0 Eisevier Science Publishers B.V. (Biom~i~aI Division)