Gamithromycin in swine: Pharmacokinetics and clinical evaluation against swine respiratory disease.

Publisher: John Wiley & Sons Ltd Country of Publication: England NLM ID: 101678837 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2053-1095 (Electronic) Linking ISSN: 20531095 NLM ISO Abbreviation: Vet Med Sci Subsets: MEDLINE

Original Publication: [Oxford] : John Wiley & Sons Ltd., [2015]-

Anti-Bacterial Agents/*pharmacokinetics ; Macrolides/*pharmacokinetics ; Respiratory Tract Infections/*veterinary ; Swine Diseases/*drug therapy; Actinobacillus Infections/drug therapy ; Actinobacillus Infections/microbiology ; Actinobacillus Infections/veterinary ; Actinobacillus pleuropneumoniae/drug effects ; Animals ; Bordetella Infections/drug therapy ; Bordetella Infections/microbiology ; Bordetella Infections/veterinary ; Bordetella bronchiseptica/drug effects ; Female ; Haemophilus Infections/drug therapy ; Haemophilus Infections/microbiology ; Haemophilus Infections/veterinary ; Haemophilus parasuis/drug effects ; Male ; Pasteurella Infections/drug therapy ; Pasteurella Infections/microbiology ; Pasteurella Infections/veterinary ; Pasteurella multocida/drug effects ; Respiratory Tract Infections/drug therapy ; Respiratory Tract Infections/microbiology ; Sus scrofa ; Swine ; Swine Diseases/microbiology

The pharmacokinetics of gamithromycin were evaluated in 26 male castrated and female crossbred swine administered gamithromycin 15% w/v (Zactran®, Boehringer Ingelheim) intravenously at 6 mg/kg bodyweight or intramuscularly at 3, 6 or 12 mg/kg bodyweight. Blood samples were collected up to Day 10 to establish the plasma profile of gamithromycin, bioavailability and dose proportionality. When administered by intramuscular injection at 6 mg/kg BWT, pharmacokinetic parameters were as follows: area under the curve until last quantifiable plasma concentration, 5.13 ± 0.957 µg*hours/ml; maximum plasma concentration, 960 ± 153 ng/ml at 5 to 15 min; terminal half-life of 94.1 ± 20.4 hr. Absolute bioavailability was 92.2%. Increase in systemic exposure was proportional to the gamithromycin dose level over the range 3-12 mg/kg BWT. No gender-related statistically significant difference in exposure was observed. For clinical evaluation of Zactran® against swine respiratory disease, 305 pigs from six commercial farms in three countries in Europe with signs associated with Actinobacillus pleuropneumoniae and/or Haemophilus parasuis and/or Pasteurella multocida and/or Bordetella bronchiseptica were used. At each site, animals were treated once in a 1:1 ratio with a single intramuscular dose of Zactran® (6 mg gamithromycin/kg bodyweight) or Zuprevo® (4% w/v tildipirosin at 4 mg/kg bodyweight; MSD Animal Health) at the recommended dose respectively. Animals were observed and scored daily for 10 consecutive days for signs of swine respiratory disease (depression, respiration and rectal temperature), and animals presenting signs of clinical swine respiratory disease (Depression Score 3 and/or Respiratory Score 3 associated with Rectal Temperature > 40.0°C) were removed from the study and considered as treatment failure. Animals which remained in the study were individually assessed for 'treatment success' or 'treatment failure' (Depression Score ≥ 1 and Rectal Temperature > 40.0°C or Respiratory Score ≥ 1 and Rectal Temperature > 40.0°C). Using a non-inferiority hypothesis test (non-inferiority margin = 0.10), the proportion of treatment successes in the Zactran® group (97%) was equivalent to or better than that in the Zuprevo® group (93%).
(© 2020 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Curr Pharm Des. 2004;10(25):3045-53. (PMID: 15544496)
J Vet Pharmacol Ther. 2012 Feb;35(1):59-66. (PMID: 21443748)
Vet Ther. 2005 Summer;6(2):203-13. (PMID: 16094567)
J Vet Pharmacol Ther. 2013 Apr;36(2):140-53. (PMID: 22500881)
J Vet Intern Med. 2013 Nov-Dec;27(6):1305-17. (PMID: 24128266)
J Dairy Sci. 2019 Jun;102(6):5501-5510. (PMID: 30928271)
Poult Sci. 2015 Sep;94(9):2066-74. (PMID: 26195808)
Poult Sci. 2013 Jun;92(6):1516-22. (PMID: 23687147)
J Vet Pharmacol Ther. 2010 Jun 1;33(3):227-37. (PMID: 20557439)
Res Vet Sci. 2014 Feb;96(1):160-3. (PMID: 24331716)
J Vet Pharmacol Ther. 2016 Apr;39(2):157-66. (PMID: 26441021)
Am J Vet Res. 2013 Jun;74(6):847-53. (PMID: 23718652)
J Antimicrob Chemother. 1985 Jul;16 Suppl A:23-34. (PMID: 3932309)
Vet Med Sci. 2021 Mar;7(2):455-464. (PMID: 33058489)
Res Vet Sci. 2014 Oct;97(2):199-203. (PMID: 25241389)
Microb Drug Resist. 2019 May;25(4):603-610. (PMID: 30562148)
J Vet Pharmacol Ther. 2017 Aug;40(4):406-410. (PMID: 28317153)
Am J Vet Res. 2011 Mar;72(3):326-30. (PMID: 21355734)
Vet Rec. 2011 Mar 5;168(9):241. (PMID: 21493573)
Anim Health Res Rev. 2011 Dec;12(2):133-48. (PMID: 22152290)
Res Vet Sci. 2002 Oct;73(2):141-4. (PMID: 12204632)
Int J Antimicrob Agents. 1999 Mar;11 Suppl 1:S15-21; discussion S31-2. (PMID: 10204635)
J Vet Pharmacol Ther. 2020 Mar;43(2):197-207. (PMID: 31872885)

Keywords: clinical efficacy; gamithromycin; pharmacokinetics; respiratory disease; swine

0 (Anti-Bacterial Agents)
0 (Macrolides)
ZE856183S0 (gamithromycin)

Date Created: 20201015 Date Completed: 20211020 Latest Revision: 20211020

20231215

PMC8025653

10.1002/vms3.375

33058489