Skip to main content
Log in

The Pharmacokinetic Properties of Topical Levocabastine

A Review

  • Review Article
  • Drug Disposition
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

The linear and predictable pharmacokinetic properties of the histamine H1-receptor antagonist levocabastine make it particularly suitable for intranasal or ocular treatment of allergic rhinoconjunctivitis. Peak plasma concentrations (Cmax) occur within 1 to 2 hours of administration of single doses of levocabastine nasal spray and eye drops (0.2mg and 0.04mg, respectively). Drug absorption is incomplete after intranasal and ocular administration, with systemic availability ranging from 60 to 80% for levocabastine nasal spray and from 30 to 60% for the eye drops. However, as the amount of levocabastine applied intranasally and ocularly is small, the levocabastine plasma concentrations achieved are extremely low, with Cmax values in the ranges 1.4 to 2.2 μ/L and 0.26 to 0.29 μg/L for intranasal and ocular administration, respectively.

Pharmacokinetic-pharmacodynamic modelling has indicated that the clinical benefits of levocabastine are predominantly mediated through local antihistaminic effects, although some systemic activity may contribute to the therapeutic efficacy of levocabastine nasal spray during long term use.

Levocabastine undergoes minimal hepatic metabolism, i.e. ester glucuronidation, and is predominantly cleared by the kidneys. Approximately 70% of parent drug is recovered unchanged in the urine. Plasma protein binding is approximately 55% and the potential for drug interactions involving binding site displacement is negligible. Furthermore, the pharmacokinetics of this agent do not appear to be influenced by either age or gender. Levocabastine nasal spray and eye drops may thus be considered suitable for the treatment of allergic rhinoconjunctivitis in a wide patient population.

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

Access this article

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

  1. Weeke ER. Epidemiology of hay fever and perennial allergic rhinitis. Monogr Allergy 1987; 21: 1–20

    PubMed  CAS  Google Scholar 

  2. White MV. The role of histamine in allergic diseases. J Allergy Clin Immunol 1990; 86: 599–605

    Article  PubMed  CAS  Google Scholar 

  3. Badhwar AK, Druce HM. Allergic rhinitis. Clin Allergy 1992; 76: 789–803

    CAS  Google Scholar 

  4. Dechant KL, Goa KL. Levocabastine: a review of its pharmacological properties and therapeutic potential as a topical antihistamine in allergic rhinitis and conjunctivitis. Drugs 1991; 41: 202–24

    Article  PubMed  CAS  Google Scholar 

  5. Vanden Bussche G. Levocabastine hydrochloride. Drugs Future 1986; 11: 841–3

    Google Scholar 

  6. Awouters F, Niemegeers C, Jansen T, et al. Levocabastine: Pharmacological profile of a highly effective inhibitor of allergic reactions. Agents Actions 1992; 35: 12–8

    Article  PubMed  CAS  Google Scholar 

  7. Van Wauwe JP. Animal pharmacology of levocabastine: a new type of H1-antihistamine well-suited for topical application. In: Mygind N, Naclerio RM, editors. Rhinoconjunctivitis: new perspectives in topical treatment of seasonal allergic rhinitis. Proceedings of the XIIIth International Congress of Allergology and Clinical Immunology, 1988 Oct; Montreux: Hogrefe & Huber Publishers, 1989: 27–34

    Google Scholar 

  8. Pécoud A, Zuber P, Kolly M. Effect of a new selective H1 receptor antagonist (levocabastine) in a nasal and conjunctival provocation test. Int Arch Allergy Appl Immunol 1987; 82: 541–3

    Article  PubMed  Google Scholar 

  9. Abelson MB, Smith LM. Levocabastine: evaluation in the histamine and compound 48/80 models of ocular allergy in humans. Ophthalmology 1988; 95: 1494–7

    PubMed  CAS  Google Scholar 

  10. Palma-Carlos AG, Palma-Carlos ML, Rombaut N. The effect of levocabastine nasal spray in nasal provocation tests. Int J Clin Pharmacol Res 1988; 8: 25–30

    PubMed  CAS  Google Scholar 

  11. Rimås M, Kjellman N-IM, Blychert L-O, et al. Topical levocabastine protects better than sodium cromoglycate and placebo in conjunctival provocation tests. Allergy 1990; 45: 18–21

    Article  PubMed  Google Scholar 

  12. Stokes TC, Feinberg G. Rapid onset of levocabastine eye-drops in histamine-induced conjunctivitis. Clin Exp Allergy 1993; 23: 791–4

    Article  PubMed  CAS  Google Scholar 

  13. Azevedo M, Castel-Branco MG, Ferrez Oliveira J, et al. Double-blind comparison of levocabastine eye drops with sodium cromoglycate and placebo in the treatment of seasonal allergic conjunctivitis. Clin Exp Allergy 1991; 21: 689–94

    Article  PubMed  CAS  Google Scholar 

  14. Palma-Carlos AG, Chieira C, Conde TA, et al. Double-blind comparison of levocabastine nasal spray with sodium cromoglycate nasal spray in the treatment of seasonal allergic rhinitis. Ann Allergy 1991; 67: 394–8

    PubMed  CAS  Google Scholar 

  15. Schata M, Jorde W, Richarz-Barthauer U. Levocabastine nasal spray better than sodium cromoglycate and placebo in the topical treatment of seasonal allergic rhinitis. J Allergy Clin Immunol 1991; 87: 873–8

    Article  PubMed  CAS  Google Scholar 

  16. Davies BH, Mullins J. Topical levocabastine is more effective than sodium cromoglycate for the prophylaxis and treatment of seasonal allergic conjunctivitis. Allergy 1993; 48: 519–24

    Article  PubMed  CAS  Google Scholar 

  17. The Livostin Study Group. A comparison of topical levocabastine and oral terfenadine in the treatment of allergic rhinoconjunctivitis. Allergy 1993; 48: 530–4

    Article  Google Scholar 

  18. Bahmer FA, Ruprecht KW. Safety and efficacy of topical levocabastine compared with oral terfenadine. Ann Allergy 1994; 72: 429–34

    PubMed  CAS  Google Scholar 

  19. Søhoel P, Freng BA, Kramer J, et al. Topical levocabastine compared with oral terfenadine for the treatment of seasonal allergic rhinoconjunctivitis. J Allergy Clin Immunol 1993; 92: 73–81

    Article  PubMed  Google Scholar 

  20. The Swedish GP Allergy Team. Topical levocabastine compared with oral loratadine for the treatment of seasonal allergic rhinoconjunctivitis. Allergy 1994; 49: 611–5

    Article  Google Scholar 

  21. Bende M, Pipkorn U. Topical levocabastine, a selective H1-antagonist in seasonal allergic rhinoconjunctivitis. Allergy 1987; 42: 512–5

    Article  PubMed  CAS  Google Scholar 

  22. Woestenborghs R, Geuens I, Lenoir H, et al. On the selectivity of some recently developed RIAs. In: Reid E, Wilson ID, editors. Methodological surveys in biochemistry and analysis. Vol. 20. Cambridge, UK: Royal Society of Chemistry, 1990: 241–6

    Google Scholar 

  23. Heykants J, Van Peer A, Woestenborghs R, et al. The pharmacokinetics and bioavailability of levocabastine (R 50547) as studied after single intravenous and oral dosing and after multiple oral dosing in healthy subjects. Unpublished report N 40324, Janssen Research Foundation, Beerse, 1984

    Google Scholar 

  24. Heykants J, Van Peer A, Woestenborghs R, et al. The absorption and plasma levels of levocabastine (R 50547) after single and multiple intranasal application of the nose spray formulation to healthy subjects. Unpublished report N 40325, Janssen Research Foundation, Beerse, 1984

    Google Scholar 

  25. Van de Velde V, Van Peer A, Woestenborghs R, et al. Comparative bioavailability of a levocabastine suspension and solution after nasal administration to healthy volunteers. Unpublished report N 62440, Janssen Research Foundation, Beerse, 1988

    Google Scholar 

  26. Heykants J, Van Peer A, Woestenborghs R, et al. The absorption and plasma levels of levocabastine (R 50547) in healthy subjects after single and multiple instillation of the eye-drop formulation. Unpublished report N 40329, Janssen Research Foundation, Beerse, 1985

    Google Scholar 

  27. Van de Velde V, Van Peer A, Woestenborghs R, et al. Bioavailability and bioequivalence of a levocabastine suspension and solution after ophthalmic administration. Unpublished report N 59216, Janssen Research Foundation, Beerse, 1987

    Google Scholar 

  28. Lücker PW, Adolph S. Medical report on the results obtained from a study for evaluating the rate of nasal absorption comparing healthy volunteers and patients with rhinitis. Unpublished report N 62426, Janssen Research Foundation, Beerse, 1986

    Google Scholar 

  29. Weinberg E. Levocabastine nasal spray in the treatment of rhinitis in asthmatic children: a double-blind comparison with placebo. Unpublished report N 62438, Janssen Research Foundation, Beerse, 1988

    Google Scholar 

  30. de Corres F, Diaz-Pardo L. Double-blind comparison of levocabastine nasal spray with sodium cromoglycate in the topical treatment of seasonal allergic rhinitis. Unpublished report N 62501, Janssen Research Foundation, Beerse, 1988

    Google Scholar 

  31. Lücker PW, Adolph S. Medical report on the results obtained from a study for evaluating the rate of conjunctival absorption comparing healthy volunteers and patients with conjunctivitis. Unpublished report N 62425, Janssen Research Foundation, Beerse, 1986b

    Google Scholar 

  32. Heykants JJP, Snoeck E, Awouters F, et al. Antihistamines. In: Van Boxtel CJ, Holford NHG, Danhof M, editors. The in vivo study of drug action. Amsterdam: Elsevier Science Publishers 1992: 337–56

    Google Scholar 

  33. Harvey RP, Schocket AL. The effect of H1-blockade on cutaneous histamine response in man. J Allergy Clin Immunol 1980; 65: 136–9

    Article  PubMed  CAS  Google Scholar 

  34. Walker J, Howarth P, Hamilton I, et al. A placebo-controlled trial of the therapeutic value of levocabastine eye drops used as required in the treatment of seasonal allergic conjunctivitis. Unpublished report, N 62497, Janssen Research Foundation, Beerse, 1988

    Google Scholar 

  35. Heykants J, Van Peer A, Woestenborghs R, et al. Pharmacokinetics and bioavailability of levocabastine (R 50547) in man. Arch Int Pharmacodyn Ther 1985; 274: 329–30

    Google Scholar 

  36. Prandota J. Clinical pharmacokinetics of changes in drug elimination in children. Dev Pharmacol Ther 1985; 8: 311–28

    PubMed  CAS  Google Scholar 

  37. Zazgornik J, Huang ML, Van Peer A, et al. Pharmacokinetics of orally administered levocabastine in patients with renal insufficiency. J Clin Pharmacol 1993; 33: 1214–8

    PubMed  CAS  Google Scholar 

  38. Wihl JÅ, Rudblad S, Kjellén H, Blychert LA. Levocabastine eye drops versus sodium cromoglycate in seasonal allergic conjunctivitis. Clin Exp Allergy 1991; 21 Suppl. 2: 37–8

    Article  PubMed  Google Scholar 

  39. Kemp JP. Antihistamines. Is there anything safe to prescribe? Ann Allergy 1992; 69: 276–80

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Heykants, J., Van Peer, A., Van de Velde, V. et al. The Pharmacokinetic Properties of Topical Levocabastine. Clin-Pharmacokinet 29, 221–230 (1995). https://doi.org/10.2165/00003088-199529040-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199529040-00002

Keywords

Navigation