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Tiir CoLticIL FoR Tosncco RESLArrCii-U.S.A., INC. March 14, 1978 MEMORANDUM ~ / TO: Drs. Hockett, Meiers, Sommers, Stone and Wyatt FROM: W.U. Gardner SUBJECT: William J. Jusko, Ph.D., The Research Foundation of New York, Buffalo, New York Continuation application No. 1079A "Tobacco-Drug Interactions" H 1(C-1 0 8 90154 of State University PROGRESS The past application proposed work on three drugs. It was found that one drug was not influenced by smoking. Phenytoin was not metabolized differently to a significant extent in smokers and nonsmokers but tended to be more variable in smokers. Theophynin was cleared more rapidly from the blood of smokers. Marihuana smokers had a similar increase clearance and when the two substances were smoked by the same person the effects tended to be additive. He has been all in all quite productive. He has comFleted a review paper on "Role of Tobacco in Pharmacokinetics:" It is a reasonably good review. It reads much better than his talk at the last SAB meeting. PROJECTION He plans to study the influence of smoking on the metabolism of prednisone, prednisolone and dexamethasone, the first ranking fifth in frequency of use he says. Nicotine and smoking increase blood cortisol levels. They are metabolized by microsomal mixed function wiftses. All of these substances have sensitive methods for quantitation. Smokers and nonsmokers will be pairedd by weight, sex, and age. A detailed protocol is submitted. Informed consent is required. Phenacetin has been extensively studied; its rapidly metabolized in cigarette smokers. He well add pipe and cigar smokers as well as passive smokers and marihuana smokers as well as controls and a group of cigarette smokers. Again a good protocol. Procainamide ant antiarrythmetic drug is N-acetylated; 50% of Americans are fast acetylators and 50% slow. Again a good protocol is submitted. Mention is made of surveillance studies on smoking and different drugs in association with different diseases and the effects of cessatioy of smoking on drug metabolism. Th°sP ^+rdjes wi_11 bP done through the Clinical Pharmaco- kinetics Laboratory at the Millard Fillmore Hospital. Finally he proposes the establishment of a "Center fcr Tobacco-Drug Research" at the Pharmacokinetics Laboratory, Millard Fillmore Hospital, Buffalo. Additional drugs will be studied in smokers and nonsmokers; the literature on the subject will be reviewed at 3-year intervals; smoking will be monitored by thio- cyanate determinations. The applicant states that be is one of the innovators of

T»r•. COUNCIL FoR TosACCO RESLARCU-U.S.A., Ixc. NK7,11089055 "population pharsscokinetics" and will bring together pathopbysiologic, genetic and other characterist4cs of the smoker nonsmoker drug interrelations and will catalogue and store pertinadt information. The budget includes $6,000 for a Nliltiwavelength Detector. The major item is for salaries. Fees for volunteers will cost over $7,000. He does have an hT3H grant and is cu-principxl investigator on another grnnt.