Pharmacokinetics and antibacterial activity of tiamulin after single and multiple oral administrations in geese

Irene Sartini; Cristina Vercelli; Beata Lebkowska-Wieruszewska; Andrzej Lisowski; Charbel Fadel; Amnart Poapolathep; Filomena Dessì; Mario Giorgi

doi:10.1016/j.vas.2023.100317

Pharmacokinetics and antibacterial activity of tiamulin after single and multiple oral administrations in geese

Vet Anim Sci. 2023 Oct 21:22:100317. doi: 10.1016/j.vas.2023.100317. eCollection 2023 Dec.

Authors

Irene Sartini¹, Cristina Vercelli², Beata Lebkowska-Wieruszewska³, Andrzej Lisowski⁴, Charbel Fadel¹, Amnart Poapolathep⁵, Filomena Dessì¹, Mario Giorgi^{1

6}

Affiliations

¹ Department of Veterinary Medicine, University of Sassari, Sassari, Italy.
² Department of Veterinary Sciences, University of Turin, Torino, Italy.
³ Department of Pharmacology, University of Life Sciences, Lublin, Poland.
⁴ Department of Biology and Animal Breeding, University of Life Sciences, Lublin, Poland.
⁵ Department of Pharmacology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, Thailand.
⁶ Department of Veterinary Sciences, University of Pisa, Via Livornese (lato monte), 56122, San Piero a Grado, Pisa, Italy.

Abstract

Tiamulin is an antibiotic approved exclusively in veterinary medicine, active against G-positive bacteria as well as Mycoplasma spp. and Leptospirae spp. The study was aimed to establish its pharmacokinetics and to evaluate drug effects on resistance in cloacal flora in vivo in geese. Eight healthy geese underwent to a two-phase longitudinal study (60 mg/kg single oral administration vs 60 mg/kg/day for 4 days) with a two-week wash-out period. Blood samples and cloacal swabs were collected at pre-assigned times. Minimal inhibitory concentration (MIC) has been evaluated for each isolated bacterial species. The pharmacokinetic parameters that significantly differed between the groups were C_max (p = 0.024), AUC_0-t (p = 0.031), AUC_0-inf (p = 0.038), t1/2_kel (p = 0.021), Cl/F (p = 0.036), and Vd/F (p = 0.012). Tiamulin exhibited a slow to moderate terminal half-life (3.13 h single; 2.62 h multiple) and a rapid absorption (1 h single; 0.5 h multiple) in geese, with an accumulation ratio of 1.8 after multiple doses. An in-silico simulation of multiple dosing did not reflect the results of the in vivo multiple dosage study. In both treatments, the MIC values were very high demonstrating a resistance (> 64 μg/ml) against tiamulin that can be present prior the drug administration for some strains, or emerge shortly after the commencing of treatment for some others.

Keywords: Goose; Oral; Pharmacodynamics; Pharmacokinetics; Tiamulin.