• 1. Simons FE, Simons KJ. The pharmacology and use of H1-receptor-antagonist drugs. N Engl J Med 1994;330:16631670.

  • 2. Khalaf AT, Li W, Jinquan T. Current advances in the management of urticaria. Arch Immunol Ther Exp (Warsz) 2008;56:103114.

  • 3. Yamamoto H, Yamada T, Kubo S, et al. Efficacy of oral olopatadine hydrochloride for the treatment of seasonal allergic rhinitis: a randomized, double-blind, placebo-controlled study. Allergy Asthma Proc 2010;31:296303.

    • Search Google Scholar
    • Export Citation
  • 4. Hsiao YH, Chen C, Willemse T. Effects of cetirizine in dogs with chronic atopic dermatitis: a randomized, double blind, placebo-controlled trial. J Vet Sci 2016;17:549553.

    • Search Google Scholar
    • Export Citation
  • 5. Knottenbelt DC. Equine formulary. St Louis: Saunders Elsevier, 2006;121124.

  • 6. Taglialatela M, Timmerman H, Annunziato L. Cardiotoxic potential and CNS effects of first-generation antihistamines. Trends Pharmacol Sci 2000;21:5256.

    • Search Google Scholar
    • Export Citation
  • 7. Tagawa M, Kano M, Okamura N, et al. Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-chlorpheniramine, a classical antihistamine. Br J Clin Pharmacol 2001;52:501509.

    • Search Google Scholar
    • Export Citation
  • 8. Hu Y, Sieck DE, Hsu WH. Why are second-generation H1-antihistamines minimally sedating? Eur J Pharmacol 2015;765:100106.

  • 9. Isomura T, Kono T, Hindmarch I, et al. Central nervous system effects of the second-generation antihistamines marketed in Japan—review of inter-drug differences using the proportional impairment ratio (PIR)-. PLoS One 2014;9:e114336.

    • Search Google Scholar
    • Export Citation
  • 10. Enomoto T, Lu HQ, Yin M, et al. Evaluation of the efficacy and safety of olopatadine and fexofenadine compared with placebo in Japanese cedar pollinosis using an environmental exposure unit. J Investig Allergol Clin Immunol 2009;19:299305.

    • Search Google Scholar
    • Export Citation
  • 11. Ohmori K, Hayashi K, Kaise T, et al. Pharmacological, pharmacokinetic and clinical properties of olopatadine hydrochloride, a new antiallergic drug. Jpn J Pharmacol 2002;88:379397.

    • Search Google Scholar
    • Export Citation
  • 12. Tanizaki H, Yamamoto Y, Nakamizo S, et al. Comparison of the efficacy of olopatadine and fexofenadine in chronic idiopathic urticaria patients: a crossover study. Pharmacology 2015;95:3235.

    • Search Google Scholar
    • Export Citation
  • 13. Wang T, Liu Y, Yin J, et al. A multicenter, double-blind, randomized, noninferiority comparison of 14 days’ treatment with oral olopatadine 10 mg or cetirizine 10 mg in Chinese adults with cutaneous pruritus. Pharmacology 2013;91:117122.

    • Search Google Scholar
    • Export Citation
  • 14. Tashiro M, Mochizuki H, Sakurada Y, et al. Brain histamine H receptor occupancy of orally administered antihistamines measured by positron emission tomography with (11)C-doxepin in a placebo-controlled crossover study design in healthy subjects: a comparison of olopatadine and ketotifen. Br J Clin Pharmacol 2006;61:1626.

    • Search Google Scholar
    • Export Citation
  • 15. Takahashi H, Zhang Y, Morita E. Evaluation of the antihistamine effects of olopatadine, cetirizine and fexofenadine during a 24 h period: a double-blind, randomized, crossover, placebo-controlled comparison in skin responses induced by histamine iontophoresis. Arch Dermatol Res 2008;300:291295.

    • Search Google Scholar
    • Export Citation
  • 16. Hinden S, Klukowska-Rötzler J, Janda J, et al. Characterization of the inflammatory infiltrate and cytokine expression in the skin of horses with recurrent urticaria. Vet Dermatol 2012;23:503e99.

    • Search Google Scholar
    • Export Citation
  • 17. Kehrli D, Jandova V, Fey K, et al. Multiple hypersensitivities including recurrent airway obstruction, insect bite hyper-sensitivity, and urticaria in 2 warmblood horse populations. J Vet Intern Med 2015;29:320326.

    • Search Google Scholar
    • Export Citation
  • 18. Kuroda T, Nagata S, Takizawa Y, et al. Pharmacokinetics and pharmacodynamics of d-chlorpheniramine following intravenous and oral administration in healthy Thoroughbred horses. Vet J 2013;197:433437.

    • Search Google Scholar
    • Export Citation
  • 19. Törneke K, Ingvast-Larsson C, Pettersson K, et al. Pharmacokinetics and pharmacodynamics of clemastine in healthy horses. J Vet Pharmacol Ther 2003;26:151157.

    • Search Google Scholar
    • Export Citation
  • 20. Olsén L, Ingvast-Larsson C, Larsson P, et al. Fexofenadine in horses: pharmacokinetics, pharmacodynamics and effect of ivermectin pretreatment. J Vet Pharmacol Ther 2006;29:129135.

    • Search Google Scholar
    • Export Citation
  • 21. Olsén L, Bondesson U, Broström H, et al. Cetirizine in horses: pharmacokinetics and pharmacodynamics following repeated oral administration. Vet J 2008;177:242249.

    • Search Google Scholar
    • Export Citation
  • 22. Knych HK, Stanley SD, Arthur RM, et al. Elimination of cetirizine following administration of multiple doses to exercised Thoroughbred horses. J Vet Pharmacol Ther 2016;39:522524.

    • Search Google Scholar
    • Export Citation
  • 23. Chu NN, Chen WL, Xu HR, et al. Pharmacokinetics of orally administered single- and multiple-dose olopatadine in healthy Chinese subjects: an open-label study. Clin Drug Investig 2009;29:451457.

    • Search Google Scholar
    • Export Citation
  • 24. Kamei H, Isaji A, Noda Y, et al. Effects of single therapeutic doses of promethazine, fexofenadine and olopatadine on psychomotor function and histamine-induced wheal- and flare-responses: a randomized double-blind, placebo-controlled study in healthy volunteers. Arch Dermatol Res 2012;304:263272.

    • Search Google Scholar
    • Export Citation
  • 25. Tsunoo M, Momomura S, Masuo M, et al. Phase I clinical study on KW-4679, an antiallergic drug. Safety and pharmacokinetics in the single and repeated administration study to healthy subjects. Kiso-to-Rinsho 1995;29:41294147.

    • Search Google Scholar
    • Export Citation
  • 26. Simons FE, Simons KJ. Clinical pharmacology of new histamine H1 receptor antagonists. Clin Pharmacokinet 1999;36:329352.

  • 27. Grant JA, Danielson L, Rihoux JP, et al. A double-blind, single-dose, crossover comparison of cetirizine, ebastine, epinastine, fexofenadine, terfenadine, and loratadine versus placebo: suppression of histamine-induced wheal and flare response for 24 h in healthy male subjects. Allergy 1999;54:700707.

    • Search Google Scholar
    • Export Citation
  • 28. Hashimoto T, Ishii N, Hamada T, et al. Effects of olopatadine hydrochloride, a histamine h(1) receptor antagonist, on histamine-induced skin responses. Dermatol Res Pract 2010;2010:e638051.

    • Search Google Scholar
    • Export Citation
  • 29. Sil A, Tripathi SK, Chaudhuri A, et al. Olopatadine versus levocetirizine in chronic urticaria: an observer-blind, randomized, controlled trial of effectiveness and safety. J Dermatolog Treat 2013;24:466472.

    • Search Google Scholar
    • Export Citation
  • 30. Toutain PL, Lees P. Integration and modelling of pharmacokinetic and pharmacodynamic data to optimize dosage regimens in veterinary medicine. J Vet Pharmacol Ther 2004;27:467477.

    • Search Google Scholar
    • Export Citation
  • 31. Louizos C, Yáñez JA, Forrest ML, et al. Understanding the hysteresis loop conundrum in pharmacokinetic/pharmacodynamic relationships. J Pharm Pharm Sci 2014;17:3491.

    • Search Google Scholar
    • Export Citation
  • 32. Vyas FI, Prakash S, Singh AJ. QTc interval prolongation by fexofenadine in healthy human volunteers and its correlation with plasma levels of fexofenadine: a demonstration of anticlockwise hysteresis. Indian J Pharmacol 2010;42:366369.

    • Search Google Scholar
    • Export Citation
  • 33. Simons FE, Silver NA, Gu X, et al. Clinical pharmacology of H1-antihistamines in the skin. J Allergy Clin Immunol 2002;110:777783.

Advertisement

Pharmacokinetics and pharmacodynamics of olopatadine following administration via nasogastric tube to healthy horses

Taisuke Kuroda DVM, PhD1, Shun-ichi Nagata DVM, PhD2, Norihisa Tamura DVM, PhD1, Hiroshi Mita DVM1, Kanichi Kusano DVM, PhD3, Fumiaki Mizobe DVM, PhD4, Yoshimasa Takizawa DVM5, Kentaro Fukuda DVM1, and Yoshinori Kasashima DVM, PhD1
View More View Less
  • 1 1Clinical Veterinary Medicine Division, Equine Research Institute, Japan Racing Association, 1400-4 Shiba, Shimotsuke-shi, Tochigi 329-0412, Japan.
  • | 2 2Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya-shi 320-0856, Tochigi 320-0856, Japan.
  • | 3 3Equine Hospital, Ritto Training Center, Japan Racing Association, 1028 Misono, Ritto-shi, Shiga 520-3085, Japan.
  • | 4 4Equine Hospital, Miho Training Center, Japan Racing Association, 2500-2 Mikoma, Miho-mura, Inashiki-gun, Ibaraki 300-0493, Japan.
  • | 5 5Central Office, Japan Racing Association, 6-11-1 Roppongi, Minato-ku, Tokyo 106-8401, Japan.

Abstract

OBJECTIVE

To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube.

ANIMALS

4 healthy adult Thoroughbreds.

PROCEDURES

Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios were calculated on the basis of measured wheal size (area) after versus before olopatadine administration.

RESULTS

Mean ± SD maximum plasma olopatadine concentration was 48.8 ± 11.0 ng/mL approximately 1.5 hours after administration. Median terminal half-life was 6.11 hours. Mean ± SD maximal effect was 88.2 ± 4.9% inhibition approximately 3.5 hours after drug delivery, and the inhibition effect remained > 80% for 12.5 hours after treatment. No signs of adverse clinical effects were observed.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested olopatadine may have a strong, long-term inhibitory effect against histamine-induced wheals in the skin of horses. Clinical research with a larger number of horses is warranted.

Abstract

OBJECTIVE

To investigate the pharmacokinetics and antihistaminic effects (pharmacodynamics) of olopatadine in a small population of healthy horses after administration via nasogastric tube.

ANIMALS

4 healthy adult Thoroughbreds.

PROCEDURES

Olopatadine (0.1 mg/kg, once) was administered via nasogastric tube. Blood samples were collected at predetermined time points for pharmacokinetic analyses of the drug in plasma. Olopatadine effects were investigated by measurement of cutaneous wheals induced by ID histamine injection (0.1 mL [10 μg]/injection) at predetermined time points. Inhibition effect ratios were calculated on the basis of measured wheal size (area) after versus before olopatadine administration.

RESULTS

Mean ± SD maximum plasma olopatadine concentration was 48.8 ± 11.0 ng/mL approximately 1.5 hours after administration. Median terminal half-life was 6.11 hours. Mean ± SD maximal effect was 88.2 ± 4.9% inhibition approximately 3.5 hours after drug delivery, and the inhibition effect remained > 80% for 12.5 hours after treatment. No signs of adverse clinical effects were observed.

CONCLUSIONS AND CLINICAL RELEVANCE

Results suggested olopatadine may have a strong, long-term inhibitory effect against histamine-induced wheals in the skin of horses. Clinical research with a larger number of horses is warranted.

Contributor Notes

Address correspondence to Dr. Kuroda (taisuke.kuroda@equinst.go.jp).