Pharmacokinetics of gamithromycin after intravenous and subcutaneous administration in pigs

Wyns, Heidi; Meyer, Evelyne; Plessers, Elke; Watteyn, Anneleen; Baere, Siegrid De; Backer, Patrick De; Croubels, Siska

doi:10.1016/j.rvsc.2013.11.012

Cited by 19 publications

(27 citation statements)

References 15 publications

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“…Consequently, the i.v. administration was chosen in our study, the authors being well aware that it is not specified by the manufacturer, but well tolerated in chicken (Watteyn et al 2013) and pig (Wyns et al 2014). …”

Section: Discussionmentioning

confidence: 99%

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Treatment with gamithromycin in foals with pneumonia: comparative efficacy and adverse effects of i.m. versus i.v. administration

Hildebrand¹,

Giguère²,

Venner³

2015

PHK

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Summary: The aim of this study was to compare the frequency of adverse reactions and efficacy of i.v. administration of gamithromycin compared to i.m. gamithromycin for the treatment of foal bronchopneumonia on a farm endemic for infections caused by Rhodococcus equi. 60 foals with bronchopneumonia and treated with gamithromycin were retrospectively divided into two treatment groups. In the foals of group 1 (n = 40) gamithromycin (6 mg/kg body weight, Zactran ® , Merial) was injected once weekly for six weeks in the semitendinosus or the semimembranosus muscle. In the foals of group 2 (n = 20) gamithromycin (6 mg/kg body weight, Zactran ® ) was injected intravenously once weekly for six weeks in the jugular veins. The animals in group 2 were also treated with rifampin (10 mg/kg, q 24 h, p.o.). Local and systemic adverse effects were evaluated daily in all foals. Foals whose pneumonia worsened were removed from the study. In the group of foals treated with gamithromycin i.m. 38 of 40 (95 %) recovered without the need to be removed from the study compared to 16 of the 20 (80 %) foals treated with gamithromycin i.v.. The frequency of adverse drug reactions differed significantly between administration routes. In the group of foals treated with Zactran ® i.m. 23 of 40 foals (58 %) showed adverse effects. 18 foals (45 %) showed signs of colic that required treatment with analgesics, and 14 (35 %) developed a marked lameness on the side of the i.m. injection. In the group of the foals who got the Zactran ® i.v. no adverse effects were observed. From these results, it can be concluded that i.v. administration of Zactran ® induces significantly fewer adverse effects than i.m. administration. However, additional studies will be necessary to determine the optimal dose and dosing interval for i.v. gamithromycin that will result in similar efficacy as that achieved after i.m. administration.

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Section: Discussionmentioning

confidence: 99%

“…In contrast, i.v. injection of Zactran ® administered to chicken (Watteyn et al 2013) and pigs (Wyns et al 2014) did not result in adverse drug reactions.…”

Section: Introductionmentioning

confidence: 85%

Treatment with gamithromycin in foals with pneumonia: comparative efficacy and adverse effects of i.m. versus i.v. administration

Hildebrand¹,

Giguère²,

Venner³

2015

PHK

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“…Therefore, accumulation of macrolide antibiotics in pulmonary compartments as in the epithelial lining fluid (ELF) and in bronchoalveolar lavage cells (BALCs) is a pharmacokinetic advantage in the treatment of pulmonary infections caused by R. equi (Mor, Vanderkolk, & Heifets, ; Peters et al., , ; Togami, Chono, & Morimoto, ). Gamithromycin (GAM) is an azalide derivative with long half‐life approved for single‐dose treatment and prevention (6 mg/kg body weight; <10 ml subcutaneous injection) of bovine and swine respiratory diseases (Giguere et al., ; Emmerich, ; Wyns et al., ; DeDonder et al., ). However, there are also reports on clinical use of GAM in other species (e.g., chicken, foals) (Berghaus et al., ; Giguere et al., ; Watteyn et al., ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals

Berlin

Randow²,

Scheuch

et al. 2017

Vet Pharm & Therapeutics

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The long-acting azalide antibiotic gamithromycin is marketed for intramuscular treatment of bovine and swine infections. Off-label use in foals leads to severe local lesions likely caused by hyperosmolality of the injected solution. We provide evidence from a pharmacokinetic study in 10 warm-blooded healthy foals for intravenous bolus injection of gamithromycin diluted in distilled water to be a safe and well tolerated alternative. By intravenous dosing, markedly higher plasma exposure and better penetration into bronchoalveolar lavage cells but lower distribution into epithelial lining fluid are achieved as after intramuscular or subcutaneous administration. Intravenously injected gamithromycin was tolerated without any adverse drug reactions. The protocols for treatment of equine pulmonary infections caused by Rhodococcus equi should be revised accordingly.

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“…At present, it is only registered for use in cattle to treat bovine respiratory disease. GAM is a long-acting antibiotic with accumulation in lung tissue as supported by its extended elimination half-life and large volume of distribution in several animal species, including turkeys (Huang, 2010;Giguère et al, 2011;Watteyn et al, 2013;Wyns et al, 2014;Watteyn et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Efficacy of gamithromycin againstOrnithobacterium rhinotrachealein turkey poults pre-infected with avian metapneumovirus

et al. 2016

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Ornithobacterium rhinotracheale is an avian respiratory pathogen that affects turkeys. The objective of this study was to evaluate the clinical efficacy of gamithromycin (GAM) against O. rhinotracheale in turkeys. The birds were inoculated oculonasally with 10 8 colony-forming units (cfu) of O. rhinotracheale, preceded by infection with avian metapneumovirus. In addition to a negative (CONTR−) and a positive control group (CONTR+) there were two treated groups administered GAM (6 mg/kg) either subcutaneously (GAM SC) or orally (GAM PO) by administration as a single bolus at one-day post-bacterial infection (p.b.i.). From the start of the avian metapneumovirus infection until the end of the experiment, the turkeys were examined clinically and scored daily. In addition, tracheal swabs were collected at several days p.b.i. Necropsy was performed at 4, 8 and 12 days p.b.i. to evaluate the presence of gross lesions, and to collect trachea and lung tissue samples and air sac swabs for O. rhinotracheale quantification. The clinical score of the GAM SC group showed slightly lower values and birds recovered earlier than those in the GAM PO and CONTR+ groups. O. rhinotracheale cfus were significantly reduced in tracheal swabs of the SC group between 2 and 4 days p.b.i. At necropsy, CONTR+ showed higher O. rhinotracheale cfu in lung tissues compared to the treated groups. Moreover, at 8 days p.b.i. only the lung samples of CONTR+ were positive. In conclusion, the efficacy of GAM against O. rhinotracheale was demonstrated, especially in the lung tissue. However, the PO bolus administration of the commercially available product was not as efficacious as the SC bolus.ARTICLE HISTORY

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Pharmacokinetics of gamithromycin after intravenous and subcutaneous administration in pigs

Cited by 19 publications

References 15 publications

Treatment with gamithromycin in foals with pneumonia: comparative efficacy and adverse effects of i.m. versus i.v. administration

Treatment with gamithromycin in foals with pneumonia: comparative efficacy and adverse effects of i.m. versus i.v. administration

Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals

Efficacy of gamithromycin againstOrnithobacterium rhinotrachealein turkey poults pre-infected with avian metapneumovirus

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