Tissue Residues and Pharmacokinetic/Pharmacodynamic Modeling of Tiamulin Against Mycoplasma anatis in Ducks

Elazab, Sara T.; Elshater, Nahla S.; Hashem, Yousreya H.; Park, Seung-Chun; Hsu, Walter H.

doi:10.3389/fvets.2020.603950

Cited by 9 publications

(12 citation statements)

References 31 publications

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“…Based on the MRL of tiamulin (100 µg/kg) in fish laid down by South Korea (37), the calculated WT values of tiamulin were 8.40 days for kidney, 8.21 days for liver, 8.07 days for gill, 7.24 days for plasma, and 4.05 days for muscle plus skin at 25 • C. The results of our study are consistent with the previous results that tiamulin in poultry and swine has a short withdrawal period (38,39,42). For example, the calculated WT was 6 days for liver and 5 days for muscle in ducks following oral administration via gavage with tiamulin at 40 mg/kg/day for 3 days at 23-27 • C (39).…”

Section: Discussionsupporting

confidence: 91%

Temperature-Dependent Residue Depletion Regularities of Tiamulin in Nile Tilapia (Oreochromis niloticus) Following Multiple Oral Administrations

et al. 2021

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The aim of this study was to investigate the effect of different water temperatures (19, 25, and 30°C) on tissue residue depletion of tiamulin in Nile tilapia (Oreochromis niloticus) after five consecutive days of oral administration at the dose of 20 mg/kg body weight and to calculate the corresponding elimination half-life (T1/2) and withdrawal times (WTs). After oral administration at scheduled 11 time points (1, 2, 3, 5, 7, 9, 12, 15, 20, 25, and 30 days), samples of plasma and tissues (muscle plus skin, liver, kidney, and gill) were collected. Tiamulin concentration in samples were determined by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). T1/2 was calculated by the equation: T1/2 = ln2/k. WT 1.4 software was used to calculate WT. The results showed that tiamulin was widely distributed in all tissue samples with the highest concentration in liver. At three different water temperatures, the T1/2 were calculated as 2.76, 2.13, and 1.64 days in plasma, 2.71, 1.85, and 1.31 days in muscle plus skin, 2.27, 1.70, and 1.50 days in liver, 2.84, 2.32, and 1.94 day in kidney, and 3.16, 2.42, and 1.74 days in gill, respectively. At 19°C, the order of WT is kidney (11.88 days) > liver (10.41 days) > gill (10.77 days) > plasma (8.83 days) > muscle plus skin (7.14 days). The WT for tiamulin at 25°C was in the following order: kidney (8.40 days) > liver (8.21 days) > gill (8.07 days) > plasma (7.24 days) > muscle plus skin (4.05 days). At 30°C, the WT dropped and shown as follows: gill (6.99 days) > kidney (6.51 days) > liver (6.29 days) > plasma (3.27 days) > muscle plus skin (2.92 days). The present investigations indicated that increasing the temperature from 19 to 30°C shortened T1/2 and WT of tiamulin in tilapia. To ensure the safety of fish consumption, the longest WT of tissues is suggested for tiamulin in Nile tilapia at the corresponding water temperature; i.e., WTs were 12 days at 19°C, 9 days at 25°C, and 7 days at 30°C, respectively. Overall, we intended to provide a theoretical basis for tissue residue depletion kinetics of tiamulin in fish and improve our understanding of the influence of the temperature on tissue residue depletion kinetics of tiamulin in fish.

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Section: Discussionsupporting

confidence: 91%

Temperature-Dependent Residue Depletion Regularities of Tiamulin in Nile Tilapia (Oreochromis niloticus) Following Multiple Oral Administrations

et al. 2021

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“…While the abundance and overall availability of in vitro and in vivo ADMET data is naturally limited to animals for the two veterinary drugs tiamulin ( 2 ), − and valnemulin ( 3 ), , the FDA approval of lefamulin ( 5 ) for systemic treatment of community acquired bacterial pneumonia in humans has yielded invaluable in vitro and in vivo data, which are primarily summarized in the Center for Drug Evaluation and Research’s Multi-Discipline Review of lefamulin ( 5 )…”

Section: Introductionmentioning

confidence: 99%

Hit-to-Lead Identification and Validation of a Triaromatic Pleuromutilin Antibiotic Candidate

Heidtmann,

Fejer,

Stærk

et al. 2024

J. Med. Chem.

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Herein, we report the hit-to-lead identification of a drug-like pleuromutilin conjugate 16, based on a triaromatic hit reported in 2020. The lead arose as the clear candidate from a hitoptimization campaign in which Gram-positive antibacterial activity, solubility, and P-gp affinity were optimized. Conjugate 16 was extensively evaluated for its in vitro ADMET performance which, apart from solubility, was overall on par with lefamulin. This evaluation included Caco-2 cell permeability, plasma protein binding, hERG inhibition, cytotoxicity, metabolism in microsomes and CYP3A4, resistance induction, and time-kill kinetics. Intravenous pharmacokinetics of 16 proved satisfactory in both mice and pigs; however, oral bioavailability was limited likely due to insufficient solubility. The in vivo efficacy was evaluated in mice, systemically infected with Staphylococcus aureus, where 16 showed rapid reduction in blood bacteriaemia. Through our comprehensive studies, lead 16 has emerged as a highly promising and safe antibiotic candidate for the treatment of Gram-positive bacterial infections.

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“…Tiamulin is a limited-spectrum antibiotic, with antibacterial properties characterised by its high activity against Gram-positive bacteria, such as staphylococci and streptococci [9,10]; a variety of mycoplasmata [9][10][11][12][13][14][15]; and spirochetes, such as Brachyspira spp. [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Determination of Tiamulin Concentration in Sow Milk and in Sera of Suckling Piglets

Cybulski,

Gajda,

Bilecka

et al. 2023

Molecules

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Although modern analytical methods developed for monitoring antibiotics in several biological matrices are easily available, none of them have been applied to evaluate the transfer of tiamulin into sow milk. Therefore, this work was intended to analyse the concentrations of tiamulin in milk samples collected from lactating sows during and after a treatment consisting of three consecutive intramuscular applications of the antibiotic. The second aim of this investigation was to determine tiamulin concentrations in serum samples obtained from suckling piglets ingesting milk contaminated with the compound. Ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) was used to quantify the analyte in both matrices. Our investigation proved tiamulin was transmitted into the milk of lactating sows. The mean concentration of the antibiotic among samples collected 3 h after administration was 1043 μg/L. The mean level of tiamulin on days 1 and 2 was 876 μg/L and 902 μg/L, respectively. The highest mean concentration of the antibiotic (1061 μg/L) was observed in samples collected on day 3. The mean concentration of the antibiotic in serum samples collected from 3-day-old piglets was 22.2 μg/L. The association between their body weight and serum tiamulin concentration was not statistically significant (p = 0.456).

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Tissue Residues and Pharmacokinetic/Pharmacodynamic Modeling of Tiamulin Against Mycoplasma anatis in Ducks

Cited by 9 publications

References 31 publications

Temperature-Dependent Residue Depletion Regularities of Tiamulin in Nile Tilapia (Oreochromis niloticus) Following Multiple Oral Administrations

Temperature-Dependent Residue Depletion Regularities of Tiamulin in Nile Tilapia (Oreochromis niloticus) Following Multiple Oral Administrations

Hit-to-Lead Identification and Validation of a Triaromatic Pleuromutilin Antibiotic Candidate

Determination of Tiamulin Concentration in Sow Milk and in Sera of Suckling Piglets

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