Skip to main content
PMC home page
Journal of Medical Toxicology logoLink to Journal of Medical Toxicology
. 2007 Jun;3(2):63–72. doi: 10.1007/BF03160911

The clinical significance of variations in ethanol toxicokinetics

Anthony F Pizon 1,✉, Charles E Becker 2, Dale Bikin 3
PMCID: PMC3550085  PMID: 18072163

Abstract

Introduction

Many variables affect the interpretation of an isolated ethanol level in an acutely intoxicated patient. This review demonstrates the significant variability in metabolism and elimination of ethanol, how it can differ between individuals, and the clinical importance of these variables.

Discussion

Isolated ethanol values in a clinical scenario are only a snapshot of a dynamic process. The individual pharmacokinetic differences of people make it extremely difficult to estimate ethanol elimination rates or calculate previous ethanol concentrations at the time of an accident because of medical-legal reasons. Not only are the techniques used in measuring ethanol concentrations in bodily fluids (blood, serum, breath, and urine) not equivalent, but also the units used to report ethanol concentrations are often misinterpreted. Acute and chronic tolerance and social adaptive changes make interpreting this isolated ethanol level extremely difficult. The purpose of this review is to enable the clinician to appropriately interpret ethanol concentrations.

Conclusion

The clinical evaluation of a patient’s inebriation is always more reliable than an isolated ethanol level for determining disposition. Only an estimation of a current serum ethanol level can be made if the blood draw was performed hours earlier. This review is clinically important because it shows the clinically significant variability in metabolism and elimination of ethanol and how it can differ between individuals. It will also describe different ways to measure ethanol concentrations and how to compare them. Finally, the interpretation of isolated ethanol levels will be discussed.

Keywords: ethanol, pharmacokinetics, pharmacodynamics, laboratory analysis, tolerance

Full Text

The Full Text of this article is available as a PDF (290.2 KB).

Footnotes

There was no outside funding of any kind used for this study.

References

  • 1.Holt S, Stewart IC, Dixon JM, Elton RA, Taylor TV, Little K. Alcohol and the emergency service patient. Br Med J. 1980;281:638–640. doi: 10.1136/bmj.281.6241.638. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Waller JA. Management issues for trauma patients with alcohol. J Trauma. 1990;30:1548–1553. doi: 10.1097/00005373-199012000-00020. [DOI] [PubMed] [Google Scholar]
  • 3.Goldberg L. Quantitative studies on alcohol tolerance in man. Acta Physiol Scand. 1943;5(16):1–128. [Google Scholar]
  • 4.Kechagias S, Jonsson KA, Norlander B, Carlsson B, Jones AW. Low-dose aspirin decreases blood alcohol concentrations by delaying gastric emptying. Eur J Clin Pharmacol. 1997;31:241–246. doi: 10.1007/s002280050369. [DOI] [PubMed] [Google Scholar]
  • 5.Levitt MD, Levitt DG. The critical role of the rate of ethanol absorption in the interpretation of studies purporting to demonstrate gastric metabolism of ethanol. L Pharmacol Exp Ther. 1994;269:297–304. [PubMed] [Google Scholar]
  • 6.Johnson RD, Horowitz M, Maddox AF, Wishart JM, Shearman DJ. Cigarette smoking and rate of gastric emptying: effect of alcohol absorption. BMJ. 1991;302:20–23. doi: 10.1136/bmj.302.6767.20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Schwartz JG, Salman UA, McMahan CA, Phillips WT. Gastric emptying of beer in Mexican-American compared with non-Hispanic whites. Metabolism. 1996;45:1174–1178. doi: 10.1016/S0026-0495(96)90019-0. [DOI] [PubMed] [Google Scholar]
  • 8.Klockhoff H, Naslund I, Jones AW. Faster absorption of ethanol and higher peak concentration in women after gastric bypass surgery. Br J Clin Pharmacol. 2002;54:587–591. doi: 10.1046/j.1365-2125.2002.01698.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Edelbroek MA, Horowitz M, Wishart JM, Akkermans LM. Effects of erythromycin on gastric emptying, alcohol absorption and small intestinal transit in normal subjects. J Nucl Med. 1993;34:582–588. [PubMed] [Google Scholar]
  • 10.Amir I, Anwar N, Baraona E, Lieber CS. Ranitidine increases the bioavailability of imbibed alcohol by accelerating gastric emptying. Life Sci. 1996;58:511–518. doi: 10.1016/0024-3205(95)02316-X. [DOI] [PubMed] [Google Scholar]
  • 11.Frezza M, DiPadova C, Pozzato G, Terpin M, Baraona E, Lieber CS. High blood alcohol levels in women: The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med. 1990;322:95–99. doi: 10.1056/NEJM199001113220205. [DOI] [PubMed] [Google Scholar]
  • 12.Jones BM, Hones MK. Alcohol effects in women during the menstrual cycle. Ann NY Acad Sci. 1976;273:576–587. doi: 10.1111/j.1749-6632.1976.tb52931.x. [DOI] [PubMed] [Google Scholar]
  • 13.Marshall AW, Kinstone D, Boss M, Morgan MY. Ethanol elimination in males and females: relationship in menstrual cycle and body composition. Hepatology. 1983;3:701–706. doi: 10.1002/hep.1840030513. [DOI] [PubMed] [Google Scholar]
  • 14.Mumenthaler MS, Tayler JL, Yesavage JA. Ethanol pharmacokinetics in white women: nonlinear model fitting versus zero-order elimination analyses. Alcohol Clin Exp Res. 2000;24:1353–1362. doi: 10.1111/j.1530-0277.2000.tb02103.x. [DOI] [PubMed] [Google Scholar]
  • 15.Haddad L, Milke P, Zapata L, de la Fuente JR, Vargas-Vorackova F, Lorenzana-Jimenez M, et al. Effect of the menstrual cycle in ethanol pharmacokinetics. J Appl Toxicol. 1998;18:15–18. doi: 10.1002/(SICI)1099-1263(199801/02)18:1<15::AID-JAT463>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  • 16.Endres HG, Bruner O. Comparison of D2O and ethanol dilutions in total body water measurements in humans. Clin Investig. 1994;72:830–837. doi: 10.1007/BF00190736. [DOI] [PubMed] [Google Scholar]
  • 17.Cowan JM, Weathermon A, McCutcheon JR, Oliver RD. Determination of volume of distribution for ethanol in male and female subjects. J Anal Toxicol. 1996;20:287–290. doi: 10.1093/jat/20.5.287. [DOI] [PubMed] [Google Scholar]
  • 18.Norberg A, Jones AW, Hahn RG, Gabrielsson JL. Role of variability in explaining ethanol pharmacokinetics. Clin Pharmacokinet. 2003;42:1–31. doi: 10.2165/00003088-200342010-00001. [DOI] [PubMed] [Google Scholar]
  • 19.Derr RF. Simulation studies on ethanol metabolism in different human populations with a physiological pharmacokinetic model. J Pharm Sci. 1993;82:677–682. doi: 10.1002/jps.2600820702. [DOI] [PubMed] [Google Scholar]
  • 20.Lieber CS. The discovery of the microsomal ethanol oxidizing system and its physiologic and pathologic role. Drug Metab Rev. 2004;36:511–529. doi: 10.1081/DMR-200033441. [DOI] [PubMed] [Google Scholar]
  • 21.Nomura F, Pikkarainen PH, Jauhonen P, Arai M, Gordon ER, Baraona E, Lieber CS. Effect of ethanol administration on the metabolism of ethanol in baboons. J Pharmacol Exp Ther. 1983;227:78–83. [PubMed] [Google Scholar]
  • 22.Brennan DF, Betzelos S, Reed R, Falk JL. Ethanol elimination rates in an ED population. Am J Emerg Med. 1995;13:276–280. doi: 10.1016/0735-6757(95)90199-X. [DOI] [PubMed] [Google Scholar]
  • 23.Case GA, Distefano S, Logan BK. Tabulation of alcohol content on beer and malt beverages. J Anal Toxicol. 2000;24:202–210. doi: 10.1093/jat/24.3.202. [DOI] [PubMed] [Google Scholar]
  • 24.Rainey RM. Relation between serum and whole-blood ethanol concentrations. Clin Chem. 1983;39:2288–2292. [PubMed] [Google Scholar]
  • 25.Jones AW, Hahn RG, Stalberg HP. Distribution of ethanol and water between plasma and whole blood; inter-and intra-individual variations after administration of ethanol by intravenous infusion. Scand J Clin Lab Invest. 1990;50:775–780. doi: 10.3109/00365519009091072. [DOI] [PubMed] [Google Scholar]
  • 26.Forney RB, Hughes RW, Harger RN, Richards AB. Alcohol distribution in the vascular system: Concentration of orally administered alcohol in blood from various points in the vascular system, and in rebreathed air, during absorption. QJ Stud Alcohol. 1954;25:205–220. [PubMed] [Google Scholar]
  • 27.Jones AW, Norberg A, Hahn RG. Concentration-time profiles of ethanol in arterial and venous blood and end-expired breath during and after intravenous infusion. J Forensic Sci. 1997;42:1088–1094. [PubMed] [Google Scholar]
  • 28.Winek CL, Carfagna M. Comparison of plasma, serum, and whole blood ethanol concentrations. J Anal Toxicol. 1987;11:267–268. doi: 10.1093/jat/11.6.267. [DOI] [PubMed] [Google Scholar]
  • 29.Gullberg RG. Methodology and quality assurance in forensic breath alcohol analysis. Forensic Sci Rev. 2000;12:50–68. [PubMed] [Google Scholar]
  • 30.Hlastala MP. The alcohol breath test — a review. J Appl Physiol. 1998;84:401–408. doi: 10.1063/1.368080. [DOI] [PubMed] [Google Scholar]
  • 31.Simpson G. Accuracy and precision of breath-alcohol measurements for a random subject in the postabsorptive state. Clin Chem. 1987;33:261–268. [PubMed] [Google Scholar]
  • 32.Norberg A, Gabrielsson J, Jones AW, Hahn RG. Within- and between-subject variations in pharmacokinetic parameters of ethanol by analysis of breath, venous blood and urine. Br J Clin Pharmacol. 2000;49:399–408. doi: 10.1046/j.1365-2125.2000.00194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Jones AW, Anderson L. Comparison of ethanol concentrations in venous blood and end-expired breath during a controlled drinking study. Forensic Sci Int. 2002;132:18–25. doi: 10.1016/S0379-0738(02)00417-6. [DOI] [PubMed] [Google Scholar]
  • 34.Jones AW, Beylich KM, Bjorneboe A, Ingum J, Morland J. Measuring ethanol in blood and breath for legal purposes: Variability between laboratories and between breath-test instruments. Clin Chem. 1992;38:743–747. [PubMed] [Google Scholar]
  • 35.Jones AW. Electrochemical measurement of breathalcohol concentration: Precision and acuracy in relation to blood levels. Clin ChimActa. 1985;146:175–183. doi: 10.1016/0009-8981(85)90056-7. [DOI] [PubMed] [Google Scholar]
  • 36.Jones AW. Role of rebreathing in determination of the blood-breath ratio of expired ethanol. J Appl Physiol. 1983;55:1237–1241. doi: 10.1152/jappl.1983.55.4.1237. [DOI] [PubMed] [Google Scholar]
  • 37.Degutis LC, Rabinovici R, Sabbaj A, Mascia R, Onofrio G. The saliva strip test is an accurate method to determine blood alcohol concentration in trauma patients. Acad Emerg Med. 2004;11:885–887. doi: 10.1111/j.1553-2712.2004.tb00775.x. [DOI] [PubMed] [Google Scholar]
  • 38.Christopher TA, Zeccardi JA. Evaluation of the Q.E.D. saliva alcohol test: A new, rapid, accurate device for measuring ethanol in saliva. Ann Emerg Med. 1992;21:1135–1137. doi: 10.1016/S0196-0644(05)80659-6. [DOI] [PubMed] [Google Scholar]
  • 39.Keim ME, Bartfield JM, Raccio-Robak N. Blood ethanol estimation: A comparison of three methods. Acad Emerg Med. 1996;3:85–87. doi: 10.1111/j.1553-2712.1996.tb03311.x. [DOI] [PubMed] [Google Scholar]
  • 40.Bendtsen P, Hultberg J, Carlsson M, Jones AW. Monitoring ethanol exposure in a clinical setting by analysis of blood, breath, saliva, and urine. Alcohol Clin Exp Res. 1999;23:1446–1451. [PubMed] [Google Scholar]
  • 41.Jones AW. Reference limits for urine/blood ratios of ethanol in two successive voids from drinking drivers. J Anal Toxicol. 2002;26:333–339. doi: 10.1093/jat/26.6.333. [DOI] [PubMed] [Google Scholar]
  • 42.Lane BP, Lieber CS. Ultrastructural alterations in human hepatocytes following ingestion of ethanol with adequate diets. Am J Pathol. 1966;49:593–603. [PMC free article] [PubMed] [Google Scholar]
  • 43.Iseri OA, Lieber CS, Gottlief LS. The ultrastructure of fatty liver induced by prolonged ethanol ingestion. Am J Pathol. 1966;48:535–555. [PMC free article] [PubMed] [Google Scholar]
  • 44.Tsutsumi M, Lasker JM, Shimizu M, Rosman AS, Lieber CS. The intralobular distribution of ethanol-inducible P450IIE1 in rat and human liver. Hepatology. 1989;10:437–446. doi: 10.1002/hep.1840100407. [DOI] [PubMed] [Google Scholar]
  • 45.Salaspuro MP, Lieber CS. Non-uniformity of blood ethanol elimination: its exaggeration after chronic consumption. Ann Clin Res. 1978;10:294–297. [PubMed] [Google Scholar]
  • 46.Khanna JM, Morato BS, Kalant H. Effect of NMDA antagonists, an NMDA agonist, and serotonin depletion on acute tolerance to ethanol. Pharmacol Biochem Behav. 2002;72:291–298. doi: 10.1016/S0091-3057(01)00773-0. [DOI] [PubMed] [Google Scholar]
  • 47.Martz A, Dietrich RA, Harris RA. Behavioral evidence for the involvement of gamma-aminobutyric acid in the actions of ethanol. Eur J Pharmacol. 1983;89:53–62. doi: 10.1016/0014-2999(83)90607-6. [DOI] [PubMed] [Google Scholar]
  • 48.Tabakoff B, Cornell N, Hoffman PL. Alcohol tolerance. Ann Emerg Med. 1986;15:1005–1012. doi: 10.1016/S0196-0644(86)80119-6. [DOI] [PubMed] [Google Scholar]
  • 49.Mellanby E. Alcohol: Its absorption into and disappearance from the blood under different conditions. London: HMSO; 1919. [Google Scholar]
  • 50.Mirsky IA, Piker P, Rosenbaum M, Lederer H. Adaptation of the central nervous system to varying concentrations of alcohol in the blood. Quart J Stud Alcohol. 1941;2:35–45. [Google Scholar]
  • 51.Wang MQ, Nicholson ME, Mahoney BS, Li Y, Perko MA. Proprioceptive responses under rising and falling BACs: A test of the Mellanby effect. Percept Mot Skills. 1993;77:83–88. doi: 10.2466/pms.1993.77.1.83. [DOI] [PubMed] [Google Scholar]
  • 52.Martin CS, Moss HB. Measurement of acute tolerance to alcohol in human subjects. Alcohol Clin Exp Res. 1993;17:211–216. doi: 10.1111/j.1530-0277.1993.tb00751.x. [DOI] [PubMed] [Google Scholar]
  • 53.Kaplan HL, Sellers EM, Hamilton C, Naranjo CA, Dorian P. Is there acute tolerance to alcohol at steady state? J Stud Alcohol. 1985;46:253–256. doi: 10.15288/jsa.1985.46.253. [DOI] [PubMed] [Google Scholar]
  • 54.Hiltunen AF, Saxon L, Skagerberg S, Borg S. Acute tolerance during intravenous infusion of alcohol: Comparison of performance during ascending and steady state concentrations — a pilot study. Alcohol. 2000;22:69–74. doi: 10.1016/S0741-8329(00)00107-5. [DOI] [PubMed] [Google Scholar]
  • 55.Radlow R. A quantitative theory of acute tolerance to alcohol. Psychopharmacol. 1994;114:1–8. doi: 10.1007/BF02245438. [DOI] [PubMed] [Google Scholar]
  • 56.Radlow R, Hurst RM. Temporal relations between blood alcohol concentration and alcohol effect: An experiment with human subjects. Psychpharmacol. 1985;85:260–266. doi: 10.1007/BF00428184. [DOI] [PubMed] [Google Scholar]
  • 57.Marco CA, Kelen GD. Acute intoxication. Emerg Med Clin North Am. 1990;8:731–748. [PubMed] [Google Scholar]

Articles from Journal of Medical Toxicology are provided here courtesy of Springer

RESOURCES