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Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys

Turkeys’ body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for resistan...

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Autores principales: Poźniak, Błażej, Tikhomirov, Marta, Bobrek, Kamila, Jajor, Paweł, Świtała, Marcin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467158/
https://www.ncbi.nlm.nih.gov/pubmed/34572639
http://dx.doi.org/10.3390/antibiotics10091057
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author Poźniak, Błażej
Tikhomirov, Marta
Bobrek, Kamila
Jajor, Paweł
Świtała, Marcin
author_facet Poźniak, Błażej
Tikhomirov, Marta
Bobrek, Kamila
Jajor, Paweł
Świtała, Marcin
author_sort Poźniak, Błażej
collection PubMed
description Turkeys’ body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for resistance. The study aimed to investigate whether a non-linear dosage based on a published allometric model for tylosin clearance, may optimize the internal exposure in growing turkeys. The single dose PK study was performed on turkeys aged 6, 9.5, 13 and 17 weeks (BW from 1.75 kg to 15.75 kg). Tylosin was administered intravenously (i.v.) or orally (p.o.) according to following protocols: Dose = 31.6 × BW(0.58) or Dose = 158 × BW(0.58), respectively. Plasma tylosin was measured using high-performance liquid chromatography and non-compartmental PK analysis was performed. The area under the curve (AUC(last)) after i.v. administration was 8.90 ± 1.01; 7.51 ± 1.11; 6.54 ± 1.20 and 8.01 ± 1.75 mg × h/L in 6-; 9.5-; 13- and 17-week-old turkeys, respectively. After p.o. administration AUC(last) was 4.80 ± 2.92; 4.60 ± 2.45; 3.00 ± 1.49 and 3.24 ± 2.00 mg × h/L in respective age groups indicating high variability. For i.v. administration, the non-linear dosage allowed to minimize the age-dependent variability in AUC. However, due to low oral bioavailability (8–12%) and resulting interindividual variability, the proposed approach may not improve tylosin efficacy in turkeys under farm conditions.
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spelling pubmed-84671582021-09-27 Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys Poźniak, Błażej Tikhomirov, Marta Bobrek, Kamila Jajor, Paweł Świtała, Marcin Antibiotics (Basel) Article Turkeys’ body weight (BW) increases 10-fold within only 2.5 months, leading to a change in the pharmacokinetics (PK) of drugs according to allometric principles. Thus, the same dosage may lead to age-dependent variability in efficacy, in particular, to treatment failure and/or selection for resistance. The study aimed to investigate whether a non-linear dosage based on a published allometric model for tylosin clearance, may optimize the internal exposure in growing turkeys. The single dose PK study was performed on turkeys aged 6, 9.5, 13 and 17 weeks (BW from 1.75 kg to 15.75 kg). Tylosin was administered intravenously (i.v.) or orally (p.o.) according to following protocols: Dose = 31.6 × BW(0.58) or Dose = 158 × BW(0.58), respectively. Plasma tylosin was measured using high-performance liquid chromatography and non-compartmental PK analysis was performed. The area under the curve (AUC(last)) after i.v. administration was 8.90 ± 1.01; 7.51 ± 1.11; 6.54 ± 1.20 and 8.01 ± 1.75 mg × h/L in 6-; 9.5-; 13- and 17-week-old turkeys, respectively. After p.o. administration AUC(last) was 4.80 ± 2.92; 4.60 ± 2.45; 3.00 ± 1.49 and 3.24 ± 2.00 mg × h/L in respective age groups indicating high variability. For i.v. administration, the non-linear dosage allowed to minimize the age-dependent variability in AUC. However, due to low oral bioavailability (8–12%) and resulting interindividual variability, the proposed approach may not improve tylosin efficacy in turkeys under farm conditions. MDPI 2021-08-31 /pmc/articles/PMC8467158/ /pubmed/34572639 http://dx.doi.org/10.3390/antibiotics10091057 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Poźniak, Błażej
Tikhomirov, Marta
Bobrek, Kamila
Jajor, Paweł
Świtała, Marcin
Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys
title Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys
title_full Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys
title_fullStr Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys
title_full_unstemmed Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys
title_short Tylosin Dosage Adjustment Based on Allometric Scaling in Male Turkeys
title_sort tylosin dosage adjustment based on allometric scaling in male turkeys
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467158/
https://www.ncbi.nlm.nih.gov/pubmed/34572639
http://dx.doi.org/10.3390/antibiotics10091057
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