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Chemical Compound Review

phenacetin     N-(4-ethoxyphenyl)ethanamide

Synonyms: Daprisal, Dolostop, Emprazil, Fenidina, Fortacyl, ...
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Disease relevance of phenacetin


Psychiatry related information on phenacetin


High impact information on phenacetin


Chemical compound and disease context of phenacetin


Biological context of phenacetin

  • Metabolic activation of phenacetin in rat nasal mucosa: dose-dependent binding to the glands of Bowman [19].
  • The insensitivity of the PBT to induction except at high doses of phenacetin suggests that phenacetin deethylation is not the rate-limiting process modulating exhaled labeled CO2 in healthy subjects, and that the PBT does not generally reflect normal or induced phenacetin dealkylation rates [20].
  • In addition, there was a strong correlation (R = 0.90) between rates of ABP N-oxidation and phenacetin O-deethylation, which is considered a human genetic polymorphism [21].
  • Rheumatology clinic studies indicate that the prevalence of nephropathy in habitual consumers of phenacetin-containing compounds is higher than that for habitual consumers of aspirin alone [22].
  • In the case of phenacetin acetyl hydroxylation (acetol formation), large isotope effects [(D)k(cat) or (D)(k(cat)/K(m)) > 10] were observed, providing evidence for rate-limiting C-H bond cleavage [23].

Anatomical context of phenacetin

  • Moreover, both the ABP N-oxidation and phenacetin O-deethylation activities of human liver microsomes showed a good correlation (R = 0.72) with the levels of cytochrome P-450 immunochemically related to rat P-450ISF-G [21].
  • The results suggest that a diet containing charcoal-broiled beef enhances the metabolism of phenacetin in the gastrointestinal tract and/or during its first pass through the liver [6].
  • In particular, the 1.0% and 1.5% dose levels of antipyrine and phenacetin showed a marked proliferative effect on the urothelium [24].
  • Effects of four nonsteroidal anti-inflammatory drugs including aspirin, paracetamol, sodium salicylate and phenacetin on prolidase (PLD) activity in erythrocytes were investigated [25].
  • Here we have focussed on a previously unrecognised feature of cLBPs which descriminates between those for which there is empiral evidence for direct interaction with membranes, and those which do not [26].

Associations of phenacetin with other chemical compounds


Gene context of phenacetin

  • Moreover, CA was a competitive inhibitor of expressed CYP1A2 catalysed phenacetin O-deethylation, with the apparent Ki (0.080 mM) closely matching the apparent Km (0.082 mM) for CA 3-demethylation by the expressed enzyme [30].
  • Delavirdine, nevirapine, and efavirenz produced negligible inhibition of phenacetin O-deethylation (CYP1A2) or dextromethorphan O-demethylation (CYP2D6) [31].
  • Considering the relative abundance of the various CYPs in human liver, CYP1A2 accounts for 86% of net reaction velocity at a substrate concentration of 100 microM, while CYP2C9 becomes the primary phenacetin O-deethylase at substrate concentrations of 865 microM and higher and accounts for 31% of the net Vmax of the reaction [32].
  • PEITC competitively inhibited phenacetin O-deethylase activity catalyzed by CYP1A2 (K(i) = 4.5 +/- 1.0 microM) and coumarin 7-hydroxylase activity catalyzed by CYP2A6 (K(i) = 18.2 +/- 2.5 microM) [33].
  • Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes [34].

Analytical, diagnostic and therapeutic context of phenacetin

  • In 1968 we evaluated a study group of 623 healthy women 30 to 49 years old who had evidence of a regular intake of phenacetin, as measured by urinary excretion of its metabolites, and a matched control group of 621 women [1].
  • When charcoal-broiled beef was fed to human volunteers, who were then given phenacetin orally, the concentration of phenacetin in the plasma was lowered, but its half-life in the plasma was not changed [35].
  • Phenacetin, a high-clearance drug, was labeled as [14C-ethyl]phenacetin and used in a breath test of hepatic function [36].
  • Studies in several countries have shown that the incidence of analgesic nephropathy as an indication for dialysis and transplantation corresponds to the per capita consumption of phenacetin in compound analgesics [37].
  • Four cross-sectional studies, 1 longitudinal, and 1 case-control study have shown significant differences in prevalence of nephropathy between habitual users of phenacetin-containing analgesics and control populations [22].


  1. An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987). Dubach, U.C., Rosner, B., Stürmer, T. N. Engl. J. Med. (1991) [Pubmed]
  2. "Sinutabs" for cluster headache. Cohen, K.L. N. Engl. J. Med. (1980) [Pubmed]
  3. Drug safety: phenacetin. Macklin, A.W., Welch, R.M., Cuatrecasas, P. Science (1979) [Pubmed]
  4. N-nitrosophenacetin: its synthesis, characterization, mutagenicity, and teratogenicity. Lin, J.K., Yen, J.Y., Chang, H.W., Lin-Shiau, S.Y. J. Natl. Cancer Inst. (1984) [Pubmed]
  5. Thyrotoxicosis, cryofibrinogenemia, Sinutab Maximum Strength, and purple ears. Kellett, J. Ann. Intern. Med. (1989) [Pubmed]
  6. Enhanced phenacetin metabolism in human subjects fed charcoal-broiled beef. Conney, A.H., Pantuck, E.J., Hsiao, K.C., Garland, W.A., Anderson, K.E., Alvares, A.P., Kappas, A. Clin. Pharmacol. Ther. (1976) [Pubmed]
  7. Analgesic nephropathy and phenacetin-induced transitional cell carcinoma - analysis of 300 patients with long-term consumption of phenacetin-containing drugs. Porpáczy, P., Schramek, P. Eur. Urol. (1981) [Pubmed]
  8. The risk factors for Alzheimer's disease: a review and a hypothesis. Henderson, A.S. Acta psychiatrica Scandinavica. (1988) [Pubmed]
  9. Causes of Alzheimer's disease: paracetamol (acetaminophen) today? Amphetamines tomorrow? Jones, G.R. Med. Hypotheses (2001) [Pubmed]
  10. Analgesic abuse and personality characteristics. Hobi, V., Ladewig, D., Dubach, U.C., Miest P-Ch, n.u.l.l., Ehrensberger, T. International journal of clinical pharmacology and biopharmacy. (1976) [Pubmed]
  11. Analgesic use and chronic renal disease. Sandler, D.P., Smith, J.C., Weinberg, C.R., Buckalew, V.M., Dennis, V.W., Blythe, W.B., Burgess, W.P. N. Engl. J. Med. (1989) [Pubmed]
  12. Epidemiologic study of abuse of analgesics containing phenacetin. Renal morbidity and mortality (1968-1979). Dubach, U.C., Rosner, B., Pfister, E. N. Engl. J. Med. (1983) [Pubmed]
  13. Intestinal metabolism of phenacetin in the rat: effect of charcoal-broiled beef and rat chow. Pantuck, E.J., Hsiao, K.C., Kuntzman, R., Conney, A.H. Science (1975) [Pubmed]
  14. Inhibition of interferon-mediated induction of indoleamine 2,3-dioxygenase in mouse lung by inhibitors of prostaglandin biosynthesis. Sayama, S., Yoshida, R., Oku, T., Imanishi, J., Kishida, T., Hayaishi, O. Proc. Natl. Acad. Sci. U.S.A. (1981) [Pubmed]
  15. Species-specific activation of phenacetin into bacterial mutagens by hamster liver enzymes and identification of N-hydroxyphenacetin O-glucuronide as a promutagen in the urine. Camus, A.M., Friesen, M., Croisy, A., Bartsch, H. Cancer Res. (1982) [Pubmed]
  16. Carcinogenicity of analgesics: long-term treatment of Sprague-Dawley rats with phenacetin, phenazone, caffeine and paracetamol (acetamidophen). Johansson, S.L. Int. J. Cancer (1981) [Pubmed]
  17. Selection and characterization of human cytochrome P450 1A2 mutants with altered catalytic properties. Parikh, A., Josephy, P.D., Guengerich, F.P. Biochemistry (1999) [Pubmed]
  18. In vivo inhibition of oxidative drug metabolism by, and acute toxicity of, 1-aminobenzotriazole (ABT). A tool for biochemical toxicology. Mico, B.A., Federowicz, D.A., Ripple, M.G., Kerns, W. Biochem. Pharmacol. (1988) [Pubmed]
  19. Metabolic activation of phenacetin in rat nasal mucosa: dose-dependent binding to the glands of Bowman. Brittebo, E.B. Cancer Res. (1987) [Pubmed]
  20. Comparison of the phenacetin and aminopyrine breath tests: effect of liver disease, inducers and cobaltous chloride. Schoeller, D.A., Kotake, A.N., Lambert, G.H., Krager, P.S., Baker, A.L. Hepatology (1985) [Pubmed]
  21. Metabolic oxidation of the carcinogens 4-aminobiphenyl and 4,4'-methylene-bis(2-chloroaniline) by human hepatic microsomes and by purified rat hepatic cytochrome P-450 monooxygenases. Butler, M.A., Guengerich, F.P., Kadlubar, F.F. Cancer Res. (1989) [Pubmed]
  22. Renal disease from habitual antipyretic analgesic consumption: an assessment of the epidemiologic evidence. Buckalew, V.M., Schey, H.M. Medicine (Baltimore) (1986) [Pubmed]
  23. Rate-determining steps in phenacetin oxidations by human cytochrome P450 1A2 and selected mutants. Yun, C.H., Miller, G.P., Guengerich, F.P. Biochemistry (2000) [Pubmed]
  24. The effects of acetaminophen, antipyrine and phenacetin on rat urothelial cell proliferation. Johansson, S.L., Radio, S.J., Saidi, J., Sakata, T. Carcinogenesis (1989) [Pubmed]
  25. Kinetic study of paracetamol on prolidase activity in erythrocytes by capillary electrophoresis with Ru(bpy)(3) (2+) electrochemiluminescence detection. Yuan, J., Wei, H., Jin, W., Yang, X., Wang, E. Electrophoresis (2006) [Pubmed]
  26. Sticky-finger interaction sites on cytosolic lipid-binding proteins? Kennedy, M.W., Beauchamp, J. Cell. Mol. Life Sci. (2000) [Pubmed]
  27. CYP1A2-catalyzed conversion of dietary heterocyclic amines to their proximate carcinogens is their major route of metabolism in humans. Boobis, A.R., Lynch, A.M., Murray, S., de la Torre, R., Solans, A., Farré, M., Segura, J., Gooderham, N.J., Davies, D.S. Cancer Res. (1994) [Pubmed]
  28. Renal tubular dysfunction in patients with inflammatory bowel disease treated with aminosalicylate. Schreiber, S., Hämling, J., Zehnter, E., Howaldt, S., Daerr, W., Raedler, A., Kruis, W. Gut (1997) [Pubmed]
  29. Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2: structure-activity relationships and simulation of rate constants of individual steps in catalysis. Yun, C.H., Miller, G.P., Guengerich, F.P. Biochemistry (2001) [Pubmed]
  30. Caffeine as a probe for human cytochromes P450: validation using cDNA-expression, immunoinhibition and microsomal kinetic and inhibitor techniques. Tassaneeyakul, W., Mohamed, Z., Birkett, D.J., McManus, M.E., Veronese, M.E., Tukey, R.H., Quattrochi, L.C., Gonzalez, F.J., Miners, J.O. Pharmacogenetics (1992) [Pubmed]
  31. Inhibition of human cytochrome P450 isoforms by nonnucleoside reverse transcriptase inhibitors. von Moltke, L.L., Greenblatt, D.J., Granda, B.W., Giancarlo, G.M., Duan, S.X., Daily, J.P., Harmatz, J.S., Shader, R.I. Journal of clinical pharmacology. (2001) [Pubmed]
  32. Human cytochromes P450 mediating phenacetin O-deethylation in vitro: validation of the high affinity component as an index of CYP1A2 activity. Venkatakrishnan, K., von Moltke, L.L., Greenblatt, D.J. Journal of pharmaceutical sciences. (1998) [Pubmed]
  33. Inhibition and inactivation of human cytochrome P450 isoforms by phenethyl isothiocyanate. Nakajima, M., Yoshida, R., Shimada, N., Yamazaki, H., Yokoi, T. Drug Metab. Dispos. (2001) [Pubmed]
  34. Involvement of CYP2E1 as A low-affinity enzyme in phenacetin O-deethylation in human liver microsomes. Kobayashi, K., Nakajima, M., Oshima, K., Shimada, N., Yokoi, T., Chiba, K. Drug Metab. Dispos. (1999) [Pubmed]
  35. Effect of charcoal-broiled beef on phenacetin metabolism in man. Pantuck, E.J., Hsiao, K.C., Conney, A.H., Garland, W.A., Kappas, A., Anderson, K.E., Alvares, A.P. Science (1976) [Pubmed]
  36. A [14C]phenacetin breath test to measure hepatic function in man. Breen, K.J., Bury, R.W., Calder, I.V., Desmond, P.V., Peters, M., Mashford, M.L. Hepatology (1984) [Pubmed]
  37. Renal effects of antipyretic analgesics. Nanra, R.S. Am. J. Med. (1983) [Pubmed]
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