Skip to main content
SpringerLink
Log in

Terfenadine

A Review of its Pharmacodynamic Properties and Therapeutic Efficacy

  • Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Synopsis: Terfenadine1 is a selective H1- histamine receptor antagonist. The lack of significant terfenadine penetration into the CNS is probably responsible for its lack of CNS effects. Terfenadine neither impairs psychomotor performance nor adversely affects subjective feelings, nor enhances the depressant effects of concomitantly administered alcohol or benzodiazepines. In controlled studies, the incidence of sedation due to terfenadine was comparable with that of placebo and significantly less than that with conventional antihistamines. Clinical studies have shown terfenadine to be comparable in efficacy with other antihistamines while being superior to placebo in alleviating the symptoms of seasonal allergic rhinitis. Additionally, there is good evidence that it is similarly as effective when used in the treatment of perennial rhinitis and histamine- mediated skin diseases.

Thus, terfenadine offers a worthwhile improvement in side effect profile over ‘traditional’ antihistamines, and could well become an ‘agent of choice’ (along with other nonsedating antihistamines) in many patients in whom a histamine H1- receptor antagonist is indicated.

Pharmacodynamic Studies: Animal studies utilising in vitro receptor binding techniques have shown that terfenadine has specific H1-antihistamine activity. In vivo studies have shown terfenadine to preferentially bind to peripheral rather than central H1-histamine receptors. Since conventional antihistamines which produce sedation have greater affinities for central H1-histamine receptors, the lesser penetration of terfenadine into the CNS may be responsible for its apparent lack of CNS effects. Terfenadine was active in standard pharmacological tests in animals, including histamine-induced bronchoconstriction, lethality and skin wheals. Human studies have shown terfenadine 60mg suppresses almost 100% of the histamine-induced skin wheal response and that this suppression lasts for at least 12 hours after administration. Animal studies have indicated that terfenadine possesses minimal or no antiserotoninergic, anticholinergic or antiadrenergic activity.

As with other non-sedating antihistamines such as astemizole and mequitazine, psychomotor and visual function tests in man have shown that terfenadine does not impair psychomotor performance or adversely affect subjective feelings, in contrast to conventional antihistamines which were active in these tests. Terfenadine neither affects the EEG as sedative antihistamines are known to do, nor interacts with other depressant drugs (alcohol or benzodiazepines) to produce enhanced depressant effects.

Pharmacokinetic Studies: The kinetic properties of terfenadine have only been investigated in single-dose studies. Although radioimmunoassay has usually been used to quantitate terfenadine in plasma, when radiolabelled terfenadine was studied its absorption was greater than would be assumed based on radioimmunoassay data. The observed difference in timing between peak plasma concentrations of terfenadine and maximal effect is not due to slow or delayed absorption, as peak concentrations occur 1 to 2 hours after administration. The concentration of 14C-terfenadine equivalents in tissues appears to be dose related, with animal studies showing highest concentrations of the drug in the liver and lung, but only low concentrations in the CNS. Terfenadine undergoes rapid and extensive (99.5%) biotransformation. A carboxylic acid metabolite has been shown to possess antihistaminic activity and may play a role in the activity of terfenadine in vivo. The elimination half-life of terfenadine in healthy adults is 16 to 23 hours.

Therapeutic Trials: Terfenadine has been evaluated in clinical studies in patients with allergic rhinitis (mainly seasonal), and in histamine-related allergic dermatological disorders. Global assessment evaluations of the overall efficacy of terfenadine in alleviating the symptoms of allergic rhinitis have shown terfenadine to produce ‘good’ or ‘complete’ symptom resolution in a significantly greater percentage of patients than placebo. In comparative studies, terfenadine has been found to be equally as effective as other antihistamines. Only a few studies investigating the efficacy of terfenadine in perennial rhinitis have been published, with varying results, but an unpublished multicentre study demonstrated an equal efficacy of terfenadine and clemastine and that both drugs were significantly more effective than placebo. Similarly, terfenadine has been shown to be effective in the treatment of pruritus and skin conditions such as urticaria and eczema when associated with histamine release.

Side Effects: Although the most frequently reported adverse effect during terfenadine use has been sedation, it is important to note that this incidence (14%) is comparable with the percentage of patients reporting sedation while taking placebo in these studies. The range of the percentage of patients reporting sedation due to terfenadine, placebo or other traditional antihistamines in clinical studies was 2.2 to 20%, 4.4 to 20% and 18 to 60%, respectively. Dryness of the mouth has occurred in 2 to 5% of terfenadine-treated patients versus 4% and 3 to 8% of placebo and other antihistamine-treated patients, respectively.

Dosage and Administration: The recommended adult dosage of terfenadine is 60mg orally twice daily. In children aged 6 to 12 years the dosage is 30mg to 60mg twice daily depending upon bodyweight. In children aged 3 to 5 years, the dosage is 15mg twice daily.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agbayani, B.F.; de Guzman, F. and Roxas, J.: A comparative study of the safety and efficacy of terfenadine in perennial allergic rhinitis. Acta Medica Philippina 17: 143–151 (1981).

    Google Scholar 

  • Ahn, H.S.; Petruzzi, R.F. and Peets, E.S.: Antihistamines: Therapeutic properties and affinities for [3H] mepyramine and [3H] WB 4101 binding sites in the brain. Federation Proceedings 39: 389 (1980).

    Google Scholar 

  • Backhouse, C.I.; Brewster, B.S.; Lockhart, J.D.F.; Maneksha, S.; Purvis, C.R. and Vallé-Jones, J.: Terfenadine in allergic rhinitis. A comparative trial of a new antihistamine versus chlorpheniramine and placebo. Practitioner 226: 347–351 (1982).

    PubMed  CAS  Google Scholar 

  • Barlow, J.L.R.; Beitman, R.E. and Tsai, T.H.: Terfenadine, safety and tolerance in controlled clinical trials. Arzneimittel-Forschung 32: 1215–1217 (1982).

    PubMed  CAS  Google Scholar 

  • Baugh, R. and Calvert, R.T.: The effect of diphenhydramine alone and in combination with ethanol on histamine skin response and mental performance. European Journal of Clinical Pharmacology 12: 201–204 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Bazex, J.; Sans, B. and Rostin, M.: Comparative study of terfenadine in allergic skin of patients in France. Arzneimittel-Forschung 32: 1196–1198 (1982).

    PubMed  CAS  Google Scholar 

  • Betts, T.; Markman, D.; Debenham, S.; Mortiboy, D. and McKevitt, T.: Effects of two antihistamine drugs on actual driving performance. Brit. Med, J. 288: 281–282 (1984).

    Article  CAS  Google Scholar 

  • Brandon, M.L. and Weiner, M.: Clinical investigation of terfenadine, a non-sedating antihistamine. Annals of Allergy 44: 71–75 (1980).

    PubMed  CAS  Google Scholar 

  • Brandon, M.L. and Weiner, M.: Clinical studies of terfenadine in seasonal allergic rhinitis. Arzneimittel-Forschung 32: 1204–1205 (1982).

    PubMed  CAS  Google Scholar 

  • Brostoff, J. and Lockhart, J.D.F.: Controlled trial of terfenadine and chlorpheniramine maleate in perennial rhinitis. Postgraduate Medical Journal 58: 422–423 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Burke, J.T.: Clinical pharmacology (dose/response, duration of action, tolerance). Terfenadine one year later. Comparison of European experience. Gaz. Méd. France 90 (Suppl.): 10–11 (1983).

    Google Scholar 

  • Cerio, R. and Lessof, M.H.: Treatment of chronic idiopathic urticaria with terfenadine. Clinical Allergy 14: 139–141 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Cheng, H.C.; ReavisJr, O.K.; Munro, N.L. and Woodward, J.K.; Antihistaminic effect of terfenadine. Pharmacologist 19: 187 (1977).

    Google Scholar 

  • Cheng, H.C. and Woodward, J.K.: Antihistaminic effect of terfenadine: A new piperidine-type antihistamine. Drug Development Research 2: 181–196 (1982a).

    Article  CAS  Google Scholar 

  • Cheng, H.C. and Woodward, J.K.: A kinetic study of the antihistaminic effect of terfenadine. Arzneimittel-Forschung 32: 1160–1166 (1982b).

    PubMed  CAS  Google Scholar 

  • Clarke, C.H. and Nicholson, A.N.: Performance studies with antihistamines. Brit, J. Clin. Pharmacol. 6: 31–35 (1978).

    Article  CAS  Google Scholar 

  • Cook, C.E.; Williams, D.L.; Myers; M.; Tallent, C.R.; Leeson, G.A.; Okerholm, R.A. and Wright, G.J.: Radioimmunoassay for terfenadine in human plasma. Journal of Pharmaceutical Sciences 69: 1419–1423 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Cook, L.J. and Shuster, S.: The effect of H1 and H2 receptor antagonists on the dermographic response. Acta Dermato-Venereologica 63: 260–262 (1983).

    PubMed  CAS  Google Scholar 

  • Dugue, P.; Birnbaum, J.; Poisson, A. and Charpin, J.: Clinical studies with terfenadine in seasonal allergic rhinitis in France. Arzneimittel-Forschung 32: 1206–1208 (1982).

    PubMed  CAS  Google Scholar 

  • Dugue, P.; Charpin, J.; Orlando, J.P. and Gervais, P.: Double-blind study of the treatment of acute pollen allergy with antihistamines. Entretiens de Bichat Pitié-Salpêtrière-Thèrapeutique: 137–140 (1978).

    Google Scholar 

  • Duncan, J.S.; Kennedy, H.J. and Triger, D.R.: Treatment of pruritis due to chronic obstructive liver disease. British Medical Journal 289: 22 (1984)

    Article  PubMed  CAS  Google Scholar 

  • Falliers, C.; Buchman, E.; Buckley, C.; Segal, A.; Tinkelman, D. and Wray, B.: Terfenadine: a non-sedating antihistamine in the treatment of pollenotic rhinitis during the late summer/fall pollen season (abstract). Presented at the Annual Meeting of the European Academy of Allergology and Clinical Immunology (Brussels, 16–19 May 1984).

  • Ferguson, J.; Macdonald, K.J.S. and Kenicer, K.J.A.: Comparison of terfenadine and placebo in the treatment of chronic idiopathic urticaria. Presented at the European Society of Dermatological Research (Cambridge, January 1984).

  • Fink, M. and Irwin, P.: CNS effects of the antihistamines diphenhydramine and terfenadine (RMI 9918). Pharmakopsychiatria Neuropsychopharmakologie 12: 35–44 (1979).

    CAS  Google Scholar 

  • Fink, M. and Irwin, P.: Critical flicker-fusion frequency, EEG, and psychoactive drugs. Psychopharmacol. Bull. 17: 103 (1981).

    Google Scholar 

  • Fuentes Gonzalez, V.M.; Andrade Garcia, J.L.; Perez Martin, J. and Ortega, H.G.: Terfenadine in allergic rhinitis in children — preliminary report. Allergia 28: 13–22 (1981).

    CAS  Google Scholar 

  • Garteiz, D.A.; Hook, R.H.; Walker, B.J. and Okerholm, R.A.: Pharmacokinetics and biotransformation studies of terfenadine in man. Arzneimittel-Forschung 32: 1185–1190 (1982).

    PubMed  CAS  Google Scholar 

  • Gastpar, H. and Dieterich, H.A.: Prophylaxis of seasonal allergic rhinitis with a new antihistaminic drug. Arzneimittel-Forschung 32: 1209–1211 (1982a).

    PubMed  CAS  Google Scholar 

  • Gastpar, H. and Dieterich, H.A.: Comparative study of the efficacy and tolerance of terfenadine and clemastine in patients with seasonal allergic rhinitis. Arzneimittel-Forschung 32: 1211–1213 (1982b).

    PubMed  CAS  Google Scholar 

  • Gibson, J.P.; Huffmann, K.W. and Newberne, J.W.: Preclinical safety studies with terfenadine. Arzneimittel-Forschung 32: 1179–1184 (1982).

    PubMed  CAS  Google Scholar 

  • Guill, M.F.; Buckley, R.H.; Kemp, J.; Segal, A.T.; Shirley, L.R. and Tinkleman, D.G.: Terfenadine in the treatment of fall hay-fever in children (abstract). Presented at the 40th Annual Congress of the American College of Allergists (San Francisco, 8 April 1984).

  • Hüther, K.J.; Renftle, G.; Barraud, N.; Burke, J.T. and Koch-Weser, J.: Inhibitory activity of terfenadine on histamine-induced skin wheals in man. European Journal of Clinical Pharmacology 12: 195–199 (1977).

    Article  PubMed  Google Scholar 

  • Kagan, G.; Dabrowicki, E.; Huddlestone, L.; Kapur, T.R. and Wolstencroft, P.: A double-blind trial of terfenadine and placebo in hay fever using a substitution technique for non-responders, J. Internat. Med. Res. 8: 404–407 (1980).

    CAS  Google Scholar 

  • Kemp, J.P.; Buchman, E.; Buckley, C.E.; Chretien, J.; Foster, T.; Gershwin, M.E. and Gordon, W.: Terfenadine: new antihistamine for seasonal allergic rhinitis (abstract). Presented at the Annual Meeting of the European Academy of Allergology and Clinical Immunology (Brussels, 16–19 May 1984).

  • Kinsolving, C.R.; Munro, N.L. and Carr, A.A.: Separation of the CNS and H1 receptor effects of antihistamine agents. Pharmacologist 15: 221 (1973).

    Google Scholar 

  • Krause, L. and Shuster, S.: Mode of action of H1 antihistamines in itch. British Journal of Dermatology 109 (Suppl. 24): 30 (1983a).

    Article  Google Scholar 

  • Krause, L. and Shuster, S.: Mechanism of action of antipruritic drugs. British Medical Journal 287: 1199–1200 (1983b).

    Article  PubMed  CAS  Google Scholar 

  • Krause, L.B. and Shuster, S.: The effect of terfenadine on dermographic wealing. Brit, J. Dermatol. 110: 73–79 (1984).

    Article  CAS  Google Scholar 

  • Kulshrestha, V.K.; Gupta, P.P.; Turner, P. and Wadsworth, J.: Some clinical pharmacological studies with terfenadine, a new antihistamine drug. British Journal of Clinical Pharmacology 6:25–29 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Leeson, G.A.; Chan, K.Y.; Knapp, W.C.; Biedenbach, S.A. and Wright, G.J.: Metabolic fate of terfenadine in rats. Federation Proceedings 34: 733 (1975).

    Google Scholar 

  • Leeson, G.A.; Chan, K.Y.; Knapp, W.C.; Biedenbach, S.A.; Wright, G.J. and Okerholm, R.A.: Metabolic disposition of terfenadine in laboratory animals. Arzneimittel-Forschung 32: 1173–1178 (1982).

    PubMed  CAS  Google Scholar 

  • Lockhart, J.D.F. and Maneksha, S.: Children with allergies. Terfenadine suspension plus placebo. Practitioner 227: 1313–1315 (1983).

    PubMed  CAS  Google Scholar 

  • Loy, M.; Di Tucci, A.; Locci, F. and Del Giacco, G.S.: Use of a new antihistaminic agent (terfenadine) in allergic rhinitis. Folia Allergologica et Immunologica Clinica 28: 351–358 (1981).

    Google Scholar 

  • Luscombe, D.K.; Nicholls, P.J. and Parish, P.A.: Comparison of the effects of azatadine and terfenadine on human performance. Pharmatherapeutica 3: 370–375 (1983).

    PubMed  CAS  Google Scholar 

  • Martin, J.P. and Huerta, J.G.: A study of the tolerance and effectiveness of terfenadine suspension in children with acute allergic conditions. Mexico Congress of Allergy and Immunology, Tijuana (36th Congress), pp.32–33, 16–20 November (1981).

  • Melillo, G.; D’Amato, G.; Zanussi, C.; Ortolani, C.; Pastorello, E.; Loy, M.; Di Tucci, A.; Locci, F.; Del Giacco, G.S.; Lenzini, L.; Sestini, P. and Rottoli, P.: A multicentre controlled trial of terfenadine, dexchlorpheniramine, and placebo in allergic rhinitis. Arzneimittel-Forschung 32: 1202–1203 (1982).

    PubMed  CAS  Google Scholar 

  • Menon, A.D. and Stamm, A.C.: Clinical evaluation of a new selective H i receptor antagonist: Terfenadine. Revista Brasileira de Clinica e Terapêutica 12: 317–322 (1983).

    Google Scholar 

  • Meyer, R.L. and Garten, J.: Experiences with an expanded test during outpatient therapy with Teldane in Switzerland. Swiss Medicine 4: 52–54 (1982).

    Google Scholar 

  • Mocellin, L. and Mocellin, M.: An effective treatment of allergic rhinitis with a selective peripheral H1-receptor antagonist (terfenadine). Rev. Brasil. Clin. Terapêut. 12: 314–316 (1983).

    Google Scholar 

  • Moser, L.; Hüther, K.J.; Koch-Weser, J. and Lundt, P.V.: Effects of terfenadine and diphenhydramine alone or in combination with diazepam or alcohol on psychomotor performance and subjective feelings. Europ, J. Clin. Pharmacol. 14: 417–423 (1978).

    Article  CAS  Google Scholar 

  • Nicholson, A.N.; Smith, P.A. and Spencer, M.B.: Antihistamines and visual function: Studies on dynamic acuity and the pupillary response to light. British Journal of Clinical Pharmacology 14: 683–690 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Nicholson, A.N. and Stone, B.M.: Performance studies with the H1-histamine receptor antagonists, astemizole and terfenadine. British Journal of Clinical Pharmacology 13: 199–202 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Nicholson, A.N. and Stone, B.M.: The H1-antagonist mequitazine: Studies on performance and visual function. European Journal of Clinical Pharmacology 25: 563–566 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Niemegeers, C.J.E.; Awouters, F.H.L. and Janssen, P.A.J.: The in vivopharmacological profile of histamine (H1) antagonists in the rat. Drug Development Research 2: 559–566 (1982).

    Article  CAS  Google Scholar 

  • Okerholm, R.A.; Weiner, D.L.; Hook, R.H.; Walker, B.J.; Leeson, G.A.; Biedenbach, S.A.; Cawein, M.J.; Dusebout, T.D.; Wright, G.J.; Myers, M.; Schindler, V. and Cook, C.E.: Bioavailability of terfenadine in man. Biopharmaceutics and Drug Disposition 2: 185–190 (1981).

    Article  CAS  Google Scholar 

  • Patel, K.R.: Terfenadine in exercise induced asthma. British Medical Journal 288: 1496–1497 (1984).

    Article  PubMed  CAS  Google Scholar 

  • Reinberg, A.; Levi, F.; Guillet, P.; Burke, J.T. and Nicolai, A.: Chronopharmacological study of antihistamines in man with special references to terfenadine. European Journal of Clinical Pharmacology 14: 245–252 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Reinberg, A.; Levi, F.; Guillet, P.; Nicolai, A. and Dupont, J.: Chronopharmacologic study of antihistaminic agents, with special reference to terfenadine. Chronobiologia 4: 142–143 (1977).

    Google Scholar 

  • Rose, C.; Quach, T.T.; Llorens, C and Schwartz, J.C.: Relationship between occupation of cerebral H1-receptors and sedative properties of antihistamines. Assessment in the case of terfenadine. Arzneimittel-Forschung 32: 1171–1173 (1982).

    PubMed  CAS  Google Scholar 

  • Ruiz, E.M.; Suarez de la Torre, R.S. and Bernat, J.F.: Comparative double-blind study of the efficacy and safety of oral terfenadine as against oral dextro-chlorpheniramine in the treatment of allergic dermatosis. Investigacion Médica Internacional 7: 341–348 (1980).

    Google Scholar 

  • Shuster, S.: Reason and the rash. Proceedings of the Royal Institution of Great Britain 53: 136–163 (1981).

    Google Scholar 

  • Tanaka, T.; Yamazaki, N.; Shimura, T.; Tsuchiya, S.; Sato, S.; Kawaguchi, Y.; Saito, K.; Kogawa, K.; Mamiya, M. and Ito, H.: Subacute toxicity and recovery tests on terfenadine in rats. Kanagawa Shigaku 15: 281–322 (1980).

    Google Scholar 

  • Van Landeghem, V.H.; Burke, J.T. and Thebault, J.: The use of a human bioassay in determining the bioequivalence of two formulations of the antihistamine terfenadine. Clinical Pharmacology and Therapeutics 27: 290–291 (1980).

    Google Scholar 

  • Varonier, H.S. and Dieterich, H.A.: Terfenadine suspension versus clemastine syrup in children with acute pollinosis. Presented at the Annual Meeting of the European Academy of Allergology and Clinical Immunology (Brussels, 16–19 May 1984).

  • Warin, R.P.: The effect of large doses of H1 antagonists in urticaria. British Journal of Dermatology III: 121–126 (1984).

    Article  Google Scholar 

  • Weiner, M.: Sedation and antihistamines. Arzneimittel-Forschung 32: 1193–1195 (1982).

    PubMed  CAS  Google Scholar 

  • Wiech, N.L. and Martin, J.S.: Absence of an effect of terfenadine on guinea pig brain histamine H1-receptors in vivo determined by receptor binding techniques. Arzneimittel-Forschung 32: 1167–1170 (1982).

    PubMed  CAS  Google Scholar 

  • Woodward, J.K. and Munro, N.L.: Terfenadine, the first non-sedating antihistamine. Arzneimittel-Forschung 32: 1154–1156 (1982).

    PubMed  CAS  Google Scholar 

  • Wüthrich, B.: Experiences with Teldane in the treatment of pollinosis. Schweiz. Med. Wochen. 4: 48, 51–52 (1982).

    Google Scholar 

  • Wüthrich, B.; Gütling, M. and Jundt, Th.: Comparison of terfenadine suspension versus ketotifen syrup in children with atopic dermatitis. A double-blind study (abstract). Presented at the Annual Meeting of the European Academy of Allergology and Clinical Immunology (Brussels, 16–19 May 1984).

Download references

Author information

Authors and Affiliations

  1. ADIS Drug Information Services, P.O. Box 34-030, Birkenhead, Auckland 10, New Zealand

    E. M. Sorkin & R. C. Heel

Authors
  1. E. M. Sorkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. C. Heel
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Various sections of the manuscript reviewed by: M.L. Brandon, Allergy Medical Group of San Diego Inc., San Diego, California, U.S.A.; P. Dugué, Service de Pneumologie Phtisiologie et Allergologie, Centre Hospitalier Général de Grasse Cedex, France; M. Fink, Department of Psychiatry, State University of New York at Stony Brook School of Medicine, St James, New York, U.S.A.; H. Gastpar, Universitäts-Hals-Nasen-Ohrenklinik München, Poliklinik Innenstadt, Munich, Federal Replublic of Germany; R.T. Jackson, Division of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, U.S.A.; G. Melillo, Divisione de Pneumologia e Allergologia Respiratoria, Ospedale A. Cardarelli, Naples, Italy; N. Mygind, Rigshospitalet, Otopathological Laboratory, University Ear-Nose-Throat Department, Copenhagen, Denmark; A.N. Nicholson, RAF Institute of Aviation Medicine, Farnborough, Hampshire, England; J.S. Turner Division of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, U.S.A.; J.D. Wilson, Department of Pathology, College of Medicine and King Khalid Hospital, Riyadh, Saudi Arabia.

‘Seldane’, ‘Teldane’, ‘Triludan’ (Merrell Dow Pharmaceuticals); ‘Teldane’ (Lepetit); ‘Triludan’ (Gist-Brocades).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sorkin, E.M., Heel, R.C. Terfenadine. Drugs 29, 34–56 (1985). https://doi.org/10.2165/00003495-198529010-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-198529010-00002

Keywords

Search

Navigation