European Journal of Clinical Pharmacology

, Volume 48, Issue 2, pp 143–150

Lack of interaction between two antihistamines, mizolastine and cetirizine, and ethanol in psychomotor and driving performance in healthy subjects

  • A. Patat
  • N. Ulliac
  • I. Zieleniuk
  • D. Stubbs
  • C. Dunmore
  • B. Sexton
  • A. Irving
  • W. Jones


The pharmacodynamic interaction between mizolastine, a new H1 antihistamine, and ethanol was assessed in a randomized, double-blind, three-way crossover, placebo-controlled study. Eighteen healthy young male volunteers received mizolastine 10 mg, or cetirizine 10 mg or placebo once daily for 7 days with a 1-week wash-out interval. An oral dose of ethanol or ethanol placebo, given 2 h after dosing on days 5 or 7 of each treatment period, was administered to achieve a peak blood alcohol concentration (BAC) of 0.7 g/l, then maintained for 1 h by two further doses of ethanol. Driving ability and psychomotor performance were evaluated using actual and simulated driving tests, critical flicker fusion threshold (CFF), adaptive tracking and divided attention (DAT) tasks. Ethanol produced a significant decrement in all tasks up to 5.5 h after administration: an increase in steering movements of 4.6, in lateral deviation of 0.45 m, in braking reaction time of 80 ms, in driving test and DAT performance of +3.2; and a decrease in CFF and in tracking speed of 2.6 m·s−1. Neither mizolastine nor cetirizine significantly impaired driving ability or arousal (CFF) compared with the placebo. However, both drugs significantly impaired DAT performance 6:00 h post-dose (increase of +2.1 for mizolastine and +2.4 for cetirizine). The tracking speed was significantly decreased 7:50 h after mizolastine administration (-1.3 m·s−1) and more consistently from 1:30 to 7:50 h after cetirizine administration (-1.4 m·s−1). No significant adverse interaction, i.e potentiation, occurred between ethanol and either antihistamine. No pharmacokinetic interaction occurred in BAC. In conclusion, treatment with a therapeutic dose of mizolastine or cetirizine has minimal or no effect on human performance, does not impair driving task performance and does not interact with ethanol at concentrations of 0.7 g·−1.

Key words

Mizolastine Cetirizine Ethanol interaction psychomotor performance antihistamine 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Scatton B, Arbilla S, Allen J, Dana C, Benavides J (1990) Pharmacological properties and autoradiographic distribution of the binding of 3H-SL 85.0324, a non sedative H1 receptor antagonist, in the guinea-pig brain. Eur J Pharmacol 183:1729–1730Google Scholar
  2. 2.
    Lloyd KG, Levrier J, Duval D, Prouteau M, Berry C, Scatton B (1990) Antianaphylactic activity of the nonsedative histamine H1 receptor antagonist SL 85.0324 in the rat and guinea-pig. Eur J Pharmacol 183:218Google Scholar
  3. 3.
    Rosenzweig P, Thebault JJ, Caplain H, Dubruc C, Bianchetti G, Fuseau E, Morselli PL (1992) Pharmacodynamics and pharmacokinetics of mizolastine (SL 85.0324), a new nonsedative H1 antihistamine. Ann Allergy 69:135–139Google Scholar
  4. 4.
    Rosenzweig P, Ulliac N, Cabanis MJ (1994) Comparative wheal and flare study of mizolastine versus terfenadine, cetirizine, loratadine and placebo in healthy volunteers. Br J Clin Pharmacol 37:116PGoogle Scholar
  5. 5.
    Danjou Ph, Molinier P, Berlin I, Patat A, Rosenzweig P, Morselli PL (1992) Assessment of the anticholinergic effects of the new antihistamine mizolastine in healthy subjects. Br J Clin Pharmacol 34:328–331Google Scholar
  6. 6.
    Kerr JS, Dunmore C, Hindmarch I (1994) The psychomotor and cognitive effects of a new antihistamine, mizolastine, compared to terfenadine, triprolidine and placebo in healthy volunteers. Eur J Pharmacol 47:331–335Google Scholar
  7. 7.
    Schaffler K, Wauschkuhn CH, Zander KJ, Bianchetti G, Kyrein HJ, Eich FX, Kauert G, Danjou Ph, Rosenzweig P (1990) CNS-pharmacodynamics and pharmocokinetics of the new non-sedative H1-antihistamine SL 85.0324 vs placebo and dimetinden in volunteers. Eur J Pharmacol 183:595–596Google Scholar
  8. 8.
    Vuurman E, Uiterwijk M, Rosenzweig P, O'Hanlon JF (1994) Effects of mizolastine and clemastine in actual driving and psychomotor performance in healthy volunteers. Eur J Clin Pharmacol 47:253–259Google Scholar
  9. 9.
    Simons FER (1994) H1-receptor antagonists. Comparative tolerability and safety. Drug Safety 10:350–380Google Scholar
  10. 10.
    Simons FER, Simons KJ (1994) The pharmacology and use of H1-receptor antagonists. N Engl J Med 330:1663–1670Google Scholar
  11. 11.
    Simons FER (1994) The therapeutic index of newer H1-receptor antagonists. Clin Exp Allergy 24:707–723Google Scholar
  12. 12.
    Clarke CH, Nicholson AN (1978) Performance studies with antihistamines. Br J Clin Pharmacol 6:31–35Google Scholar
  13. 13.
    Nicholson AN, Stone BM (1982) Performance studies with the H1-antihistamine receptor antagonists, astemizole and terfenadine. Br J Clin Pharmacol 13:199–202Google Scholar
  14. 14.
    Hindmarch I, Bhatti JZ (1987) Psychomotor effects of astemizole and chlopheniramine, alone and in combination with alcohol. Int Clin Psychopharmacol 2:117–119Google Scholar
  15. 15.
    Bhatti JZ, Hindmarch I (1989) The effect of terfenadine with and without alcohol on an aspect of car driving performance. Clin Exp Allergy 16:609–611Google Scholar
  16. 16.
    Bateman DN, Chapman PH, Rawlins MD (1983) Lack of effect of astemizole on ethanol dynamics or kinetics. Eur J Clin Pharmacol 25:567–568Google Scholar
  17. 17.
    Doms M, Vanhulle G, Baelde Y, Coulie P, Dupont P, Rihoux JP (1988) Lack of potentiation by cetirizine of alcoholinduced psychomotor disturbances. Eur J Clin Pharmacol 34:619–623Google Scholar
  18. 18.
    Ramaekers JG, Uiterwijk M, O'Hanlon JF (1992) Effects of loratadine and cetirizine on actual driving and psychometric test performance and EEG during driving. Eur J Clin Pharmacol 42:363–369Google Scholar
  19. 19.
    Mattila MJ, Kuitunen T, Plétan Y (1992) Lack of pharmacodynamic and pharmacokinetic interactions of the antihistamine ebastine with ethanol in healthy subjects. Eur J Clin Pharmacol 43:179–184Google Scholar
  20. 20.
    Irving A, Jones W (1992) Methods for testing impairment of driving due to drugs. Eur J Clin Pharmacol 43:61–66Google Scholar
  21. 21.
    Campoli-Richard DM, Buckley MM, Fitton A (1990) Cetirizine a review of its pharmacological properties and clinical potential in allergic rhinitis, pollen-induced asthma and chronic urticaria. Drugs 40:762–781Google Scholar
  22. 22.
    Spencer CM, Faulds D, Peters DH (1993) Cetirizine: a reappraisal of its pharmacological properties and therapeutic use in selected allergic disorders. Drugs 46:1055–1080Google Scholar
  23. 23.
    Irving A (1988) A proposed investigation into Drug Impairment Testing Methodology. In: Burley D, Silvestone T (eds) Medicine and road traffic safety. CNS (Clinical Neuro Science) publishers, London, pp 99–110Google Scholar
  24. 24.
    O'Hanlon JF (1984) Driving performance under the influence of drugs, a rationale for, and application of, a new test. Br J Clin Pharmacol 18 [Suppl]:121S-129SGoogle Scholar
  25. 25.
    Borland RG, Nicholson AN (1984) Visual motor co-ordination and dynamic visual acuity. Br J Clin Pharmacol 18 [Suppl]:69S-72SGoogle Scholar
  26. 26.
    Olch RJ, Hect SE (1979) Microcomputer graphics in psychological research. Behav Res Meth Instrum 11:119–126Google Scholar
  27. 27.
    Ascalone V, Guinebault P, Rouchouse A (1993) Determination of mizolastine, a new antihistaminic drug, in human plasma by liquid-liquid extraction, solid-phase extraction and column-switching techniques in combination with high-performance liquid chromatography. J Chromatogr Biomed Appl 619:275–284Google Scholar
  28. 28.
    Simons KJ, Watson WTA, Chen XY, Simons FER (1989) Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly. Clin Pharmacol Ther 45:9–14Google Scholar
  29. 29.
    Starmer GA, Bird KD (1984) Investigating drug-ethanol interactions. Br J Clin Pharmacol 18 [Suppl]:27S-35SGoogle Scholar
  30. 30.
    Starmer GA (1990) Alcohol and car driving: impairment and per se limits for drivers. In Hindmarch I, Stonier P (eds) Human psychopharmacology: methods and measures, vol 3. Wiley, Chichester, pp 184–201Google Scholar
  31. 31.
    Mattila MJ, Mattila ME, Nuotto E (1993) Measuring drugalcohol and drug-drug interactions of psychotropic drugs on human skilled performance. In: Hindmarch I, Stonier P (eds) Human psychopharmacology: methods and measures, vol 4. Wiley, Chichester, pp 165–194Google Scholar
  32. 32.
    Louwerens JW, Gloerich ABM, de Vries G, Brookhuis KA, O'Hanlon JF (1987) The relationship between drivers' blood alcohol concentration (BAC) and actual driving performance during high speed travel. In: Noordzij PZ, Roszbach R (eds) Alcohol, drugs and traffic safety. Excerpta Medica, Amsterdam, pp 183–186Google Scholar
  33. 33.
    Hindmarch I, Kerr JS, Sherwood N (1991) The effects of alcohol and other drugs on psychomotor performance and cognitive function. Alcohol Alcohol 26:71–79Google Scholar
  34. 34.
    Moskowitz H, Bwins M, Williams AF (1985) Skill performance at low blood alcohol levels. J Stud Alcohol 46:482–485Google Scholar
  35. 35.
    Patat A, Gram LF, Dubruc C, Brohier S, Cabanis MJ, Rosenzweig P (1994) Effects of mizolastine, a new antihistamine, on psychomotor performance and memory in elderly subjects. Int Clin Psychopharmacol 9:101–108Google Scholar
  36. 36.
    Patat A, Perault MC, Vandel B, Ulliac N, Zieleniuk I, Rosenzweig P (1995) Lack of interaction between a new antihistamine, mizolastine, and lorazepam on psychomotor performance and memory in healthy volunteers. Br J Clin Pharmacol 39:31–38Google Scholar
  37. 37.
    Riedel WJ, Van Veggel L, O'Hanlon J (1990) Cetirizine 10 and 20 mg impair psychomotor performance. Clin Exp Allergy 20 [Suppl]: 97Google Scholar
  38. 38.
    Betts TA, Kenwood C, Dalby G, Hull B, Wild J (1989) A comparison of the effects of two non-sedating antihistamines (terfenadine and cetirizine) on tests of CNS function including driving. J Psychopharmacol 3:101Google Scholar
  39. 39.
    Volkerts ER, Van Willigenburg APP, Van Laar MW, Maes RAA (1992) Does cetirizine belong to the new generation of antihistamines? An investigation into its acute and subchronic effects on highway driving, psychometric test performance and daytime sleepiness. Hum Psychopharmacol 7:227–238Google Scholar
  40. 40.
    Betts TA, Edson AE, Furlong PL (1991) The effects of single doses of 120 mg and 240 mg of terfenadine on driving and other measures of psychomotor performance including visual evoked responses. Ann Allergy 66:98Google Scholar
  41. 41.
    Meltzer EO (1991) Comparative safety of H1 antihistamines. Ann Allergy 67:625–633Google Scholar
  42. 42.
    Rombaud N, Hindmarch I (1994) Psychometric aspects of antihistamine: a review. Hum Psychopharmacol 9:157–169Google Scholar
  43. 43.
    Riedel WJ, Ramaekers JG, Uiterwijk M, O'Hanlon JF (1990) Higher doses of terfenadine and loratadine; acute and subchronic effects on psychomotor and actual driving performance. Institute for Drugs, Safety and Behavior, University of Limburg, The Netherlands, Technical report, IGVG 90–08Google Scholar
  44. 44.
    Pechardre JC, Vernay D, Trolese JF, Bloom M, Dupont P (1988) Comparison of the central and peripheral effects of cetirizine and terfenadine. Eur J Clin Pharmacol 35:255–259Google Scholar
  45. 45.
    Pechardre JC, Beudin P, Eschalier A, Trolese JF, Rihoux JP (1991) A comparison of central and peripheral effects of cetirizine and loratadine. J Int Med Res 19:285–295Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • A. Patat
    • 1
  • N. Ulliac
    • 1
  • I. Zieleniuk
    • 1
  • D. Stubbs
    • 2
  • C. Dunmore
    • 2
  • B. Sexton
    • 3
  • A. Irving
    • 3
  • W. Jones
    • 3
  1. 1.Synthélabo Recherche, Clinical Research DepartmentBagneux CedexFrance
  2. 2.Synthélabo RechercheLondonUK
  3. 3.Transport Research LaboratoryCrowthorneUK
  4. 4.Biotrial, 20, Rue du Pr. Jean PeckerTechnopole Atalante VillejeanRennesFrance

Personalised recommendations