Skip to main content

Drug Interactions with Tobacco Smoking

An Update

Clinical Pharmacokinetics volume 36, pages 425–438 (1999)Cite this article

Abstract

Cigarette smoking remains highly prevalent in most countries. It can affect drug therapy by both pharmacokinetic and pharmacodynamic mechanisms. Enzymes induced by tobacco smoking may also increase the risk of cancer by enhancing the metabolic activation of carcinogens.

Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for the induction of cytochrome P450 (CYP) 1A1, CYP1A2 and possibly CYP2E1. CYP1A1 is primarily an extrahepatic enzyme found in lung and placenta. There are genetic polymorphisms in the inducibility of CYP1A1, with some evidence that high inducibility is more common in patients with lung cancer. CYP1A2 is a hepatic enzyme responsible for the metabolism of a number of drugs and activation of some procarcinogens. Caffeine demethylation, using blood clearance or urine metabolite data, has been used as an in vivo marker of CYP1A2 activity, clearly demonstrating an effect of cigarette smoking. CYP2E1 metabolises a number of drugs as well as activating some carcinogens. Our laboratory has found in an intraindividual study that cigarette smoking significantly enhances CYP2E1 activity as measured by the clearance of chlorzoxazone.

In animal studies, nicotine induces the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown. Similarly, although inhibitory effects of the smoke constituents carbon monoxide and cadmium on CYP enzymes have been observed in vitro and in animal studies, the relevance of this inhibition to humans has not yet been established.

The mechanism involved in most interactions between cigarette smoking and drugs involves the induction of metabolism. Drugs for which induced metabolism because of cigarette smoking may have clinical consequence include theophylline, caffeine, tacrine, imipramine, haloperidol, pentazocine, propranolol, flecainide and estradiol. Cigarette smoking results in faster clearance of heparin, possibly related to smoking-related activation of thrombosis with enhanced heparin binding to antithrombin III. Cutaneous vasoconstriction by nicotine may slow the rate of insulin absorption after subcutaneous administration.

Pharmacodynamic interactions have also been described. Cigarette smoking is associated with a lesser magnitude of blood pressure and heart rate lowering during treatment with β-blockers, less sedation from benzodiazepines and less analgesia from some opioids, most likely reflecting the effects of the stimulant actions of nicotine.

The impact of cigarette smoking needs to be considered in planning and assessing responses to drug therapy. Cigarette smoking should be specifically studied in clinical trials of new drugs.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

49,54 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Hoffmann D, Djordjevic MV, Hoffmann I. The changing cigarette. Prev Med 1997; 26: 427–34.

    PubMed  CAS  Article  Google Scholar 

  2. Schumacher JN, Green CR, Best FW, et al. An extensive investigation of the water-soluble portion of cigarette smoke. J Agric Food Chem 1977; 25: 310–20.

    PubMed  CAS  Article  Google Scholar 

  3. Conney AH. Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G.H.A. Clowes Memorial Lecture. Cancer Res 1982; 42: 4875–917.

    PubMed  CAS  Google Scholar 

  4. Guengerich FP, Shimada T, Iwasaki M, et al. Activation of carcinogens by human liver cytochromes P-450. Basic Life Sci 1990; 53: 381–96.

    PubMed  CAS  Google Scholar 

  5. Ikawa S, Uematsu F, Watanabe K, et al. Assessment of cancer susceptibility in humans by use of genetic polymorphisms in carcinogen metabolism. Pharmacogenetics 1995; 5 (Spec. No): S154–60.

    PubMed  Article  Google Scholar 

  6. Gonzalez FJ. The molecular biology of cytochrome P450s. Pharmacol Rev 1988; 40: 243–88.

    PubMed  CAS  Google Scholar 

  7. Guengerich FP. Metabolic activation of carcinogens. Pharmacol Ther 1992; 54: 17–61.

    PubMed  CAS  Article  Google Scholar 

  8. McManus ME, Burgess WM, Veronese ME, et al. Metabolism of 2-acetylaminofluorene and benzo(a)pyrene and activation of food-derived heterocyclic amine mutagens by human cytochromes P-450. Cancer Res 1990; 50: 3367–76.

    PubMed  CAS  Google Scholar 

  9. Wrighton SA, VandenBranden M, Ring BJ. The human drug metabolizing cytochromes P450. J Pharmacokinet Biopharm 1996; 24: 461–73.

    PubMed  CAS  Google Scholar 

  10. Denissenko MF, Pao A, Tang M, et al. Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in P53. Science 1996; 274: 430–2.

    PubMed  CAS  Article  Google Scholar 

  11. Phillips DH, Hewer A, Martin CN, et al. Correlation of DNA adduct levels in human lung with cigarette smoking. Nature 1988; 336: 790–2.

    PubMed  CAS  Article  Google Scholar 

  12. McLemore TL, Adelberg S, Liu MC, et al. Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke-induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas. J Natl Cancer Inst 1990; 82: 1333–9.

    PubMed  CAS  Article  Google Scholar 

  13. Anttila S, Hietanen E, Vainio H, et al. Smoking and peripheral type of cancer are related to high levels of pulmonary cytochrome P450IA in lung cancer patients. Int J Cancer 1991; 47: 681–5.

    PubMed  CAS  Article  Google Scholar 

  14. Kouri RE, McKinney CE, Slomiany DJ, et al. Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res 1982; 42: 5030–7.

    PubMed  CAS  Google Scholar 

  15. Catteau A, Douriez E, Beaune P, et al. Genetic polymorphism of induction of CYP1A1 (EROD) activity. Pharmacogenetics 1995; 5: 110–9.

    PubMed  CAS  Article  Google Scholar 

  16. Willey JC, Coy EL, Frampton MW, et al. Quantitative RT-PCR measurement of cytochromes P450 1A1, 1B1, and 2B7, microsomal epoxide hydrolase, and NADPH oxidoreductase expression in lung cells of smokers and nonsmokers. Am J Respir Cell Mol Biol 1997; 17: 114–24.

    PubMed  CAS  Google Scholar 

  17. Murray BP, Edwards RJ, Murray S, et al. Human hepatic CYP1A1 and CYP1A2 content, determined with specific anti-peptide antibodies, correlates with the mutagenic activation of PhIP. Carcinogenesis 1993; 14: 585–92.

    PubMed  CAS  Article  Google Scholar 

  18. Reyes H, Reisz-Porszasz S, Hankinson O. Identification of the Ah receptor nuclear translocator protein (Arnt) as a component of the DNA binding form of the Ah receptor. Science 1992; 256: 1193–5.

    PubMed  CAS  Article  Google Scholar 

  19. Hoffmann EC, Reyes H, Chu FF, et al. Cloning of a factor required for activity of the Ah (dioxin) receptor. Science 1991; 252: 954–8.

    Article  Google Scholar 

  20. Kubota M, Sogawa K, Kaizu Y, et al. Xenobiotic responsive element in the 5′-upstream region of the human P450c gene. J Biochem (Tokyo) 1991; 110: 232–6.

    CAS  Google Scholar 

  21. Swanson HI, Chan WK, Bradfield CA. DNA binding specificities and pairing rules of the Ah receptor, ARNT, and SIM proteins. J Biol Chem 1995; 270: 26292–302.

    PubMed  CAS  Article  Google Scholar 

  22. Nebert DW. Drug metabolism and signal transduction: possible role of Ah receptor and arachidonic acid cascade in protection from ethanol toxicity. Experientia 1994; 71 Suppl.: 231–40.

    Google Scholar 

  23. Nebert DW, Petersen DD, Puga A. Human AH locus polymorphism and cancer: inducibility of CYP1A1 and other genes by combustion products and dioxin. Pharmacogenetics 1991; 1: 68–78.

    PubMed  CAS  Article  Google Scholar 

  24. Johnson BS, Brooks BA, Reyes H, et al. An MspI RFLP in the human ARNT gene, encoding a subunit of the nuclear form of the Ah (dioxin) receptor. Hum Mol Genet 1992; 1: 351.

    PubMed  CAS  Article  Google Scholar 

  25. Jacquet M, Lambert V, Baudoux E, et al. Correlation between P450 CYP1A1 inducibility, MspI genotype and lung cancer incidence. Eur J Cancer 1996; 32A: 1701–6.

    PubMed  CAS  Article  Google Scholar 

  26. Tefre T, Ryberg D, Haugen A, et al. Human CYP1A1 (cytochrome P(1)450) gene: lack of association between the MspI restriction fragment length polymorphism and incidence of lung cancer in a Norwegian population. Pharmacogenetics 1991; 1: 20–5.

    PubMed  CAS  Article  Google Scholar 

  27. Rannug A, Alexandrie AK, Persson I, et al. Genetic polymorphism of cytochromes P450 1A1, 2D6 and 2E1: regulation and toxicological significance. J Occup Environ Med 1995; 37: 25–36.

    PubMed  CAS  Article  Google Scholar 

  28. Raunio H, Husgafvel Pursiainen K, Anttila S, et al. Diagnosis of polymorphisms in carcinogen-activating and inactivating enzymes and cancer susceptibility: areview. Gene 1995; 159: 113–21.

    PubMed  CAS  Article  Google Scholar 

  29. Nakachi K, Imai K, Hayashi S, et al. Genetic susceptibility to squamous cell carcinoma of the lung in relation to cigarette smoking dose. Cancer Res 1991; 51: 5177–80.

    PubMed  CAS  Google Scholar 

  30. Kawajiri K, Nakachi K, Imai K, et al. The CYPlAl gene and cancer susceptibility. Crit Rev Oncol Hematol 1993; 14: 77–87.

    PubMed  CAS  Article  Google Scholar 

  31. Hayashi S, Watanabe J, Nakachi K, et al. Genetic linkage of lung cancer-associated MspI polymorphisms with amino acid replacement in the heme binding region of the human cytochrome P450IA1 gene. J Biochem Tokyo 1991; 110: 407–11.

    PubMed  CAS  Google Scholar 

  32. Nimura Y, Yokoyama S, Fujimori M, et al. Genotyping of the CYP1A1 and GSTM1 genes in esophageal carcinoma patients with special reference to smoking. Cancer 1997; 80: 852–7.

    PubMed  CAS  Article  Google Scholar 

  33. Hayashi S, Watanabe J, Kawajiri K. High susceptibility to lung cancer analyzed in terms of combined genotypes of P450IA1 and Mu-class glutathione S-transferase genes. Jpn J Cancer Res 1992; 83: 866–70.

    PubMed  CAS  Article  Google Scholar 

  34. Ishibe N, Wiencke JK, Zuo ZF, et al. Susceptibility to lung cancer in light smokers associated with CYPlAl polymorphisms in Mexican- and African-Americans. Cancer Epidemiol Biomarkers Prev 1997; 6: 1075–80.

    PubMed  CAS  Google Scholar 

  35. Sugimura H, Hamada GS, Suzukil, et al. CYP1A1 and CYP2E1 polymorphism and lung cancer, case-control study in Rio de Janeiro, Brazil. Pharmacogenetics 1995; 5 Spec. No.: S145–8.

    Article  Google Scholar 

  36. Meyer UA. Overview of enzymes of drug metabolism. J Pharmacokinet Biopharm 1996; 24: 449–59.

    PubMed  CAS  Google Scholar 

  37. Eaton DL, Gallagher EP, Bammler TK, et al. Role of cytochrome P4501A2 in chemical carcinogenesis: implications for human variability in expression and enzyme activity. Pharmacogenetics 1995; 5: 259–74.

    PubMed  CAS  Article  Google Scholar 

  38. Quattrochi LC, Tukey RH. The human cytochrome CYP1A2 gene contains regulatory elements responsive to 3-methylcholanthrene. Mol Pharmacol 1989; 36: 66–71.

    PubMed  CAS  Google Scholar 

  39. Quattrochi LC, Vu T, Tukey RH. The human cytochrome CYP1A2 gene and induction by 3-methylcholanthrene. Aregion of DNA that supports AH-receptor binding and promoter-specific induction. J Biol Chem 1994; 269: 6949–54.

    PubMed  CAS  Google Scholar 

  40. Butler MA, Lang NP, Young JF, et al. Determination of CYP1A2 and NAT2 phenotypes in human populations by analysis of caffeine urinary metabolites. Pharmacogenetics 1992; 2: 116–27.

    PubMed  CAS  Article  Google Scholar 

  41. Kalow W, Tank BK. Use of caffeine metabolite ratios to explore CYP1A2 and xanthine oxidase activities. Clin Pharmacol Ther 1991; 50: 508–19.

    PubMed  CAS  Article  Google Scholar 

  42. Tang BK, Kalow W. Assays for CYP1A2 by testing in vivo metabolism of caffeine in humans. Methods Enzymol 1996; 272: 124–31.

    PubMed  CAS  Article  Google Scholar 

  43. Schweikl H, Taylor JA, Kitareewan S, et al. Expression of CYP1Al and CYP1A2 genes in human liver. Pharmacogenetics 1993; 3: 239–49.

    PubMed  CAS  Article  Google Scholar 

  44. Nakajima M, Yokoi T, Mizutani M, et al. Phenotyping of CYP1A2 in Japanese population by analysis of caffeine urinary metabolites: absence of mutation prescribing the phenotype in the CYP1A2 gene. Cancer Epidemiol Biomarkers Prev 1994; 3: 413–21.

    PubMed  CAS  Google Scholar 

  45. Fuhr U, Rost KL. Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva. Pharmacogenetics 1994; 4: 109–16.

    PubMed  CAS  Article  Google Scholar 

  46. Guengerich FP, Kim DH, Iwasaki M. Role of human cytochrome P450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem Res Toxicol 1991; 4: 168–79.

    PubMed  CAS  Article  Google Scholar 

  47. Girre C, Lucas D, Hispard E, et al. Assessment of cytochrome P4502E1 induction in alcoholic patients by chlorzoxazone pharmacokinetics. Biochem Pharmacol 1994; 47: 1503–8.

    PubMed  CAS  Article  Google Scholar 

  48. Lucas D, Menez C, Girre C, et al. Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects. Pharmacogenetics 1995; 5: 298–304.

    PubMed  CAS  Article  Google Scholar 

  49. O’shea D, Davis SN, Kim RB, et al. Effect of fasting and obesity in humans on the 6-hydroxylation of chlorzoxazone: a putative probe of CYP2E1 activity. Clin Pharmacol Ther 1994; 56: 359–67.

    PubMed  Article  Google Scholar 

  50. Uematsu F, Kikuchi H, Motomiya M, et al. Human cytochrome P450IIE1 gene: DraI polymorphism and susceptibility to cancer. Tohoku J Exp Med 1992; 168: 113–7.

    PubMed  CAS  Article  Google Scholar 

  51. Villard PH, Seree EM, Lacarelle B, et al. Effect of cigarette smoke on hepatic and pulmonary cytochromes P450 in mouse: evidence for CYP2E1 induction in lung. Biochem Biophys Res Commun 1994; 202: 1731–7.

    PubMed  CAS  Article  Google Scholar 

  52. Villard PH, Herber R, Seree E, et al. Effect of cigarette smoke on UDP-glucuronosyltransferase activity and cytochrome P450 content in liver, lung and kidney microsomes in mice. Pharmacol Toxicol 1998; 82: 74–9.

    PubMed  CAS  Article  Google Scholar 

  53. Seree EM, Villard PH, Re JL, et al. High inducibility of mouse renal CYP2E1 gene by tobacco smoke and its possible effect on DNA single strand breaks. Biochem Biophys Res Commun 1996; 219: 429–34.

    PubMed  CAS  Article  Google Scholar 

  54. Benowitz NL, Jacob III P, Saunders S, et al. Carbon monoxide, cigarette smoking and CYP2E1 activity [abstract]. Clin Pharmacol Ther 1999; 63: 154.

    Article  Google Scholar 

  55. Burchell B, Brierley CH, Rance D. Specificity of human UDP-glucuronosyltransferases and xenobiotic glucuronidation. Life Sci 1995; 57: 1819–31.

    PubMed  CAS  Article  Google Scholar 

  56. Bock KW, Frohling W, Remmer H, et al. Effects of phenobarbital and 3-methylcholanthrene on substrate specificity of rat liver microsomal UDP-glucuronyltransferase. Biochim Biophys Acta 1973; 327: 46–56.

    PubMed  CAS  Article  Google Scholar 

  57. Fleischmann R, Remmer H, Starz U. Induction of cytochrome P-448 isoenzymes and related glucuronyltransferases in the human liver by cigarette smoking. Eur J Clin Pharmacol 1986; 30: 475–80.

    PubMed  CAS  Article  Google Scholar 

  58. Grech Belanger O, Gilbert M, Turgeon J, et al. Effect of cigarette smoking on mexiletine kinetics. Clin Pharmacol Ther 1985; 37: 638–43.

    PubMed  CAS  Article  Google Scholar 

  59. Bock KW, Schrenk D, Forster A, et al. The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine and paracetamol as probes. Pharmacogenetics 1994; 4: 209–18.

    PubMed  CAS  Article  Google Scholar 

  60. Walle T, Walle UK, Cowart TD, et al. Selective induction of propranolol metabolism by smoking: additional effects on renal clearance of metabolites. J Pharmacol Exp Ther 1987; 241: 928–33.

    PubMed  CAS  Google Scholar 

  61. Ochs HR, Greenblatt DJ, Otten H. Disposition of oxazepam in relation to age, sex and cigarette smoking. Klin Wochenschr 1981; 59: 899–903.

    PubMed  CAS  Article  Google Scholar 

  62. Benowitz NL, Jacob III P. Nicotine and cotinine elimination pharmacokinetics in smokers and nonsmokers. Clin Pharmacol Ther 1993; 53: 316–23.

    PubMed  CAS  Article  Google Scholar 

  63. Zevin S, Jacob III P, Benowitz NL. Cotinine effects on nicotine metabolism. Clin Pharmacol Ther 1997; 61: 649–54.

    PubMed  CAS  Article  Google Scholar 

  64. Anandatheerthavarada HK, Williams JF, Wecker L. The chronic administration of nicotine induces cytochrome P450 in rat brain. J Neurochem 1993; 60: 1941–4.

    PubMed  CAS  Article  Google Scholar 

  65. Anandatheerthavarada HK, Williams JF, Wecker L. Differential effect of chronic nicotine administration on brain cytochrome P4501A1/2 and P4502E1. Biochem Biophys Res Commun 1993; 194: 312–8.

    PubMed  CAS  Article  Google Scholar 

  66. Montgomery MR, Rubin RJ. The effect of carbon monoxide inhalation on in vivo drug metabolism in the rat. J Pharmacol Exp Ther 1971; 179: 465–73.

    PubMed  CAS  Google Scholar 

  67. Takano T, Motohashi Y, Miyazaki Y. Direct effect of carbon monoxide on hexo-barbital metabolism in the isolated perfused liver in the absence of hemoglobin. J Toxicol Environ Health 1985; 15: 847–54.

    PubMed  CAS  Article  Google Scholar 

  68. Leemann T, Bonnabry P, Dayer P. Selective inhibition of major drug metabolizing cytochrome P450 isozymes in human liver microsomes by carbon monoxide. Life Sci 1994; 54: 951–6.

    PubMed  CAS  Article  Google Scholar 

  69. Trela BA, Carlson GP, Mayer PR. Effect of carbon monoxide on the cytochrome P-450-mediated metabolism of aniline and p-nitroanisol in the isolated perfused rabbit lung. J Toxicol Environ Health 1989; 27: 331–40.

    PubMed  CAS  Article  Google Scholar 

  70. Alexidis AN, Rekka EA, Kourounakis PN. Influence of mercury and cadmium intoxication on hepatic microsomal CYP2E and CYP3A subfamilies. Res Commun Mol Pathol Pharmacol 1994; 85: 67–72.

    PubMed  CAS  Google Scholar 

  71. Miller LG. Cigarettes and drug therapy: pharmacokinetic and pharmacodynamic considerations. Clin Pharm 1990; 9: 125–35.

    PubMed  CAS  Google Scholar 

  72. Schein JR. Cigarette smoking and clinically significant drug interactions. Ann Pharmacother 1995; 29: 1139–48.

    PubMed  CAS  Google Scholar 

  73. Benowitz NL, Gourlay SG. Cardiovascular toxicity of nicotine: implications for nicotine replacement therapy. J Am Coll Cardiol 1997; 29: 1422–31.

    PubMed  CAS  Article  Google Scholar 

  74. Benowitz NL, Jacob III P, Jones RT, et al. Interindividual variability in the metabolism and cardiovascular effects of nicotine in man. J Pharmacol Exp Ther 1982; 221: 368–72.

    PubMed  CAS  Google Scholar 

  75. Powell JR, Thiercelin JF, Vozeh S, et al. The influence of cigarette smoking and sex on theophylline disposition. Am Rev Respir Dis 1977; 116: 17–23.

    PubMed  CAS  Google Scholar 

  76. Hunt SN, Jusko WJ, Yurchak AM. Effect of smoking on theophylline disposition. Clin Pharmacol Ther 1976; 19: 546–51.

    PubMed  CAS  Google Scholar 

  77. Jusko WJ, Schentag JJ, Clark JH, et al. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther 1978; 24: 405–10.

    PubMed  CAS  Google Scholar 

  78. Miller LG. Recent developments in the study of the effects of cigarette smoking on clinical pharmacokinetics and clinical pharmacodynamics. Clin Pharmacokinet 1989; 17: 90–108.

    PubMed  CAS  Article  Google Scholar 

  79. Pfeifer HF, Greenblatt DJ. Clinical toxicity of theophylline in relation to cigarette smoking: a report from the Boston Collaborative Drug Surveillance Program. Chest 1978; 73: 229–33.

    Article  Google Scholar 

  80. Lee BL, Benowitz NL, Jacob III P. Cigarette abstinence, nicotine gum, and theophylline disposition. Ann Intern Med 1987; 106: 553–5.

    PubMed  CAS  Google Scholar 

  81. Vistisen K, Loft S, Poulsen HE. Cytochrome P450 IA2 activity in man measured by caffeine metabolism: effect of smoking, broccoli and exercise. Adv Exp Med Biol 1991; 283: 407–11.

    PubMed  CAS  Article  Google Scholar 

  82. Rizzo N, Hispard E, Dolbeault S, et al. Impact of long-term ethanol consumption on CYP1A2 activity. Clin Pharmacol Ther 1997; 62: 505–9.

    PubMed  CAS  Article  Google Scholar 

  83. Welty D, Pool W, Woolf T, et al. The effect of smoking on the pharmacokinetics and metabolism of Cognex in healthy volunteers [abstract]. Pharm Res 1993; 10: S334.

    Google Scholar 

  84. Cognex product information. In: Physician’s desk reference. Montvale (NJ): Medical Economics, 1995: 1828.

  85. Raucy JL, Lasker JM, Lieber CS, et al. Acetaminophen activation by human liver cytochromes P450IIE1 and P450IA2. Arch Biochem Biophys 1989; 271: 270–83.

    PubMed  CAS  Article  Google Scholar 

  86. Snawder JE, Roe AL, Benson RW, et al. Loss of CYP2E1 and CYP1A2 activity as a function of acetaminophen dose: relation to toxicity [published erratum appears in Biochem Biophys Res Commun 1995; 206: 437]. Biochem Biophys Res Commun 1995; 203: 532–9.

    Article  Google Scholar 

  87. Thummel KE, Lee CA, Kunze KL, et al. Oxidation of acetaminophen to N-acetyl-p-aminobenzoquinone inline by human CYP3A4. Biochem Pharmacol 1993; 45: 1563–9.

    PubMed  CAS  Article  Google Scholar 

  88. Norman TR, Burrows GD, Maguire KP, et al. Cigarette smoking and plasma nortriptyline levels. Clin Pharmacol Ther 1977; 21: 453–6.

    PubMed  CAS  Google Scholar 

  89. Perry PJ, Browne JL, Prince RA, et al. Effects of smoking on nortriptyline plasma concentrations in depressed patients. Ther Drug Monit 1986; 8: 279–84.

    PubMed  CAS  Article  Google Scholar 

  90. Perel JM, Hurwic MJ, Kanzler MB. Pharmacodynamics of imipramine in depressed patients. Psychopharmacol Bull 1975; 11: 16–8.

    PubMed  CAS  Google Scholar 

  91. Hsyu P-H, Singh A, Giargiari TD, et al. Pharmacokinetics of bupropion and its metabolites in cigarette smokers versus nonsmokers. J Clin Pharmacol 1997; 37: 737–43.

    PubMed  CAS  Google Scholar 

  92. Spigset O, Carleborg L, Hedenmalm K, et al. Effect of cigarette smoking on fluvoxamine pharmacokinetics in humans. Clin Pharmacol Ther 1995; 58: 399–403.

    PubMed  CAS  Article  Google Scholar 

  93. Boston Collaborative Drug Surveillance Program. Clinical depression of the central nervous system due to diazepam and chlordiazepoxide in relation to cigarette smoking and age. N Engl J Med 1973; 288: 277–80.

    Article  Google Scholar 

  94. Ochs HR, Greenblatt DJ, Burstein ES. Lack of influence of cigarette smoking on triazolam pharmacokinetics. Br J Clin Pharmacol 1987; 23: 759–63.

    PubMed  CAS  Article  Google Scholar 

  95. Desmond PV, Roberts RK, Wilkinson GR, et al. No effect of smoking on metabolism of chlordiazepoxide [letter]. N Engl J Med 1979; 300: 199–200.

    PubMed  CAS  Google Scholar 

  96. Ochs HR, Greenblatt DJ, Knuchel M. Kinetics of diazepam, midazolam, and lorazepam in cigarette smokers. Chest 1985; 87: 223–6.

    PubMed  CAS  Article  Google Scholar 

  97. Norman TR, Fulton A, Burrows GD, et al. Pharmacokinetics of N-desmethyldiazepam after a single oral dose of clorazepate: the effect of smoking. Eur J Clin Pharmacol 1981; 21: 229–33.

    PubMed  CAS  Article  Google Scholar 

  98. Pantuck EJ, Pantuck CB, Anderson KE, et al. Cigarette smoking and chlorpromazine disposition and actions. Clin Pharmacol Ther 1982; 31: 533–8.

    PubMed  CAS  Article  Google Scholar 

  99. Stimmel GL, Falloon IR. Chlorpromazine plasma levels, adverse effects, and tobacco smoking: case report. J Clin Psychiatry 1983; 44: 420–2.

    PubMed  CAS  Google Scholar 

  100. Jann MW, Saklad SR, Ereshefsky L, et al. Effects of smoking on haloperidol and reduced haloperidol plasma concentrations and haloperidol clearance. Psychopharmacology (Berl) 1986; 90: 468–70.

    CAS  Article  Google Scholar 

  101. Taylor D. Pharmacokinetic interactions involving clozapine. Br J Psychiatry 1997; 171: 109–12.

    PubMed  CAS  Article  Google Scholar 

  102. Ring BJ, Catlow J, Lindsay TJ, et al. Identification of the human cytochromes P450 responsible for the in vitro formation of the major oxidative metabolites of the antipsychotic agent olanzapine. J Pharmacol Exp Ther 1996; 276: 658–66.

    PubMed  CAS  Google Scholar 

  103. Fulton B, Goa KL. Olanzapine: areview of its pharmacological properties and therapeutic efficacy in the management of schizophrenia and related psychoses. Drugs 1997; 53: 281–98.

    PubMed  CAS  Article  Google Scholar 

  104. Haring C, Meise U, Humpel C, et al. Dose-related plasma levels of clozapine: influence of smoking behaviour, sex and age. Psychopharmacology (Berl) 1989; 99 Suppl.: S38–S40.

    Article  Google Scholar 

  105. Hasegawa M, Gutierrez Esteinou R, Way L, et al. Relationship between clinical efficacy and clozapine concentrations in plasma in schizophrenia: effect of smoking. J Clin Psychopharmacol 1993; 13: 383–90.

    PubMed  CAS  Article  Google Scholar 

  106. Buhler FR, Vesanen K, Watters JT, et al. Impact of smoking on heart attacks, strokes, blood pressure control, drug dose, and quality of life aspects in the International Prospective Primary Prevention Study in Hypertension. Am Heart J 1988; 115: 282–8.

    PubMed  CAS  Article  Google Scholar 

  107. Bolli P, Buhler FR, McKenzie JK. Smoking, antihypertensive treatment benefit, and comprehensive antihypertensive treatment approach: some thoughts on the results of the International Prospective Primary Prevention Study in Hypertension. J Cardiovasc Pharmacol 1990; 16 Suppl.: S77–S80.

    Google Scholar 

  108. Wilhelmsen L, Berglund G, Elmfeldt D, et al. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. J Hypertens 1987; 5: 561–2.

    PubMed  CAS  Article  Google Scholar 

  109. Holtzman JL, Weeks CE, Kvam DC, et al. Identification of drug interactions by meta-analysis of premarketing trials: the effect of smoking on the pharmacokinetics and dosage requirements for flecainide acetate. Clin Pharmacol Ther 1989; 46: 1–8.

    PubMed  CAS  Article  Google Scholar 

  110. Huet PM, Lelorier J. Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics. Clin Pharmacol Ther 1980; 28: 208–15.

    PubMed  CAS  Article  Google Scholar 

  111. Bachmann K, Shapiro R, Fulton R, et al. Smoking and warfarin disposition. Clin Pharmacol Ther 1979; 25: 309–15.

    PubMed  CAS  Google Scholar 

  112. Cipolle RJ, Seifert RD, Neilan BA, et al. Heparin kinetics: variables related to disposition and dosage. Clin Pharmacol Ther 1981; 29: 387–93.

    PubMed  CAS  Article  Google Scholar 

  113. Rose JQ, Yurchak AM, Meikle AW, et al. Effect of smoking on prednisone, prednisolone, and dexamethasone pharmacokinetics. J Pharmacokinet Biopharm 1981; 9: 1–14.

    PubMed  CAS  Google Scholar 

  114. Crawford FE, Back DJ, Orme ML, et al. Oral contraceptive steroid plasma concentrations in smokers and nonsmokers. BMJ (Clin Res Ed) 1981; 282: 1829–30.

    CAS  Article  Google Scholar 

  115. Kanarkowski R, Tornatore KM, Gardner MJ, et al. Pharmacokinetics of single and multiple doses of ethinyl estradiol and levonorgestrel in relation to smoking. Clin Pharmacol Ther 1988; 43: 23–31.

    PubMed  CAS  Article  Google Scholar 

  116. Michnovicz JJ, Hershcopf RJ, Naganuma H, et al. Increased 2-hydroxylation of estradiol as a possible mechanism for the anti-estrogenic effect of cigarette smoking. N Engl J Med 1986; 315: 1305–9.

    PubMed  CAS  Article  Google Scholar 

  117. Kolendorf K, Bojsen J, Nielsen SL. Adipose tissue blood flow and insulin disappearance from subcutaneous tissue. Clin Pharmacol Ther 1979; 25: 598–604.

    PubMed  CAS  Google Scholar 

  118. Klemp P, Staberg B, Madsbad S, et al. Smoking reduces insulin absorption from subcutaneous tissue. BMJ 1982; 284: 237.

    PubMed  CAS  Article  Google Scholar 

  119. Madsbad S, McNair P, Christensen MS, et al. Influence of smoking on insulin requirement and metabolic status in diabetes mellitus. Diabetes Care 1980; 3: 41–3.

    PubMed  CAS  Article  Google Scholar 

  120. Mathiesen ER, Soegaard U, Christiansen JS. Smoking and glycaemic control in male insulin dependent (type 1) diabetics. Diabetes Res 1984; 1: 155–7.

    PubMed  CAS  Google Scholar 

  121. Johnson RD, Horowitz M, Maddox AF, et al. Cigarette smoking and rate of gastric emptying: effect on alcohol absorption. BMJ 1991; 302: 20–3.

    PubMed  CAS  Article  Google Scholar 

  122. Decreased clinical efficacy of propoxyphene in cigarette smokers. Clin Pharmacol Ther 1973; 14: 259–63.

  123. Jick H. Smoking and clinical drug effects. Med Clin North Am 1974; 58: 1143–9.

    PubMed  CAS  Google Scholar 

  124. Vaughan DP, Beckett AH, Robbie DS. The influence of smoking on the intersubject variation in pentazocine elimination. Br J Clin Pharmacol 1976; 3: 279–83.

    PubMed  CAS  Article  Google Scholar 

  125. Keeri-Szanto M, Pomeroy JR. Atmospheric pollution and pentazocine metabolism. Lancet 1971; I (7706): 947–9.

    Article  Google Scholar 

  126. Rogers JF, Findlay JW, Hull JH, et al. Codeine disposition in smokers and nonsmokers. Clin Pharmacol Ther 1982; 32: 218–27.

    PubMed  CAS  Article  Google Scholar 

  127. Yue QY, Tomson T, Sawe J. Carbamazepine and cigarette smoking induce differentially the metabolism of codeine in man. Pharmacogenetics 1994; 4: 193–8.

    PubMed  CAS  Article  Google Scholar 

  128. Apseloff G, Ashton HM, Friedman H, et al. The importance of measuring cotinine levels to identify smokers in clinical trials. Clin Pharmacol Ther 1994; 56: 460–2.

    PubMed  CAS  Article  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Internal Medicine, Shaare Zedek Medical Center, Jerusalem, Israel

    Shoshana Zevin

  2. Division of Clinical Pharmacology and Experimental Therapeutics, Medical Service, San Francisco General Hospital Medical Center and the Department of Medicine and Psychiatry, University of California, Building 30, Room 3220, 1001 Potrero Avenue, San Francisco, California, 94110, USA

    Neal L. Benowitz

Authors
  1. Shoshana Zevin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neal L. Benowitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Neal L. Benowitz.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Zevin, S., Benowitz, N.L. Drug Interactions with Tobacco Smoking. Clin Pharmacokinet 36, 425–438 (1999). https://doi.org/10.2165/00003088-199936060-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199936060-00004

Keywords

  • Nicotine
  • Adis International Limited
  • Theophylline
  • Cotinine
  • Flecainide