Pharmacokinetics and pulmonary distribution of gamithromycin after intravenous administration in foals

Abstract

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.

Epidemiological and PK/PD cutoff values determination and PK/PD-based dose assessment of gamithromycin against Haemophilus parasuis in piglets

“…Gamithromycin concentrations in serum were determined by a validated HPLC-MS/MS method using an Agilent 1200 HPLC system linked to an API 4000 triple quadrupole mass spectrometer as previously reported [8,31]. In brief, serum samples (0.5 mL) were mixed with 0.5 mL of acetonitrile, followed by vortex and centrifugation at 12,000×g for 10 min.…”

Intestinal and hepatic contributions to the pharmacokinetic interaction between gamithromycin and rifampicin after single‐dose and multiple‐dose administration in healthy foals

“…Gamithromycin, decladinosyl gamithromycin (declad-gamithromycin), rifampicin, 25-O-desacetyl rifampicin (DAc-rifampicin), CHOL and 4b-OH-CHOL) were quantified in plasma, lavage fluid and BALC respectively, using validated LC-MS/MS methods as recently described [22][23][24]. The lower limits of quantification (LLOQ) were 1 and 2 ng/mL for gamithromycin and declad-gamithromycin, 2.5 ng/mL for rifampicin and DAc-rifampicin, 50 and 5 ng/mL for CHOL and 4b-OH-CHOL respectively.…”

“…On the first study day, the pharmacokinetics of rifampicin was evaluated after a single-dose administration of 10 mg/kg. Venous blood was sampled before and 0.5, 1, 2, 3,4,6,8,12,16,24,36 and 48 h after oral administration. Seven days later, the animals were treated with gamithromycin i.v.…”

“…Venous blood (each sample 5-7 mL) was collected from a jugular vein using a venous catheter (VasoVet â , G16) d . On the 29th and 43rd study day respectively, the mutual interactions between single-dose and multiple-dose rifampicin (10 mg/kg, once daily) and chronic gamithromycin (4th and 6th intravenous dosing) were evaluated by blood sampling before and 0.5, 1, 2, 3,4,6,8,12,16,24,36,48,72,120 and 168 h after administration of rifampicin. The dosing of rifampicin on the 30th study day was omitted to accurately evaluate the existing half-lives.…”

Tildipirosin: An effective antibiotic against Glaesserella parasuis from an in vitro analysis

“…1 B). These differences were not expected since macrolides, especially Tildipirosin, have an extraordinary ability to accumulate in different compartments of lung tissue and to persist in fluids surrounding the lung epithelial cells ( Berlin et al., 2017 ; Menge et al., 2012 ; Rose et al., 2013 ; Villarino et al., 2013 ).

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