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Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats
BACKGROUND: Credelio(TM) (lotilaner) is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats. It is formulated as a pure S-enantiomer in flavoured chewable tablets. The pharmacokinetics of lotilaner were investigated after intravenous...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044034/ https://www.ncbi.nlm.nih.gov/pubmed/30001724 http://dx.doi.org/10.1186/s13071-018-2966-6 |
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author | Toutain, Céline E. Seewald, Wolfgang Jung, Martin |
author_facet | Toutain, Céline E. Seewald, Wolfgang Jung, Martin |
author_sort | Toutain, Céline E. |
collection | PubMed |
description | BACKGROUND: Credelio(TM) (lotilaner) is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats. It is formulated as a pure S-enantiomer in flavoured chewable tablets. The pharmacokinetics of lotilaner were investigated after intravenous or oral administration and under fed or fasted conditions in cats. Twenty-six adult cats were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of lotilaner. Following the oral administration at a dosage of 6 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability of lotilaner was evaluated in a separate bioanalytical study. RESULTS: Following oral administration in fed cats, lotilaner was readily absorbed and peak blood concentrations reached within four hours. The terminal half-life was 33.6 days. Food enhanced the absorption, providing close to 100% oral bioavailability and reduced the inter-individual variability. Following intravenous administration, lotilaner had a low clearance of 0.13 l/kg/day, large volumes of distribution V(z) and V(ss) of 5.34 and 5.37 l/kg, respectively and a terminal half-life of 28.7 days. In addition, there was no in vivo racemization of lotilaner. CONCLUSIONS: The pharmacokinetic properties of lotilaner administered orally as a flavoured chewable tablet (Credelio(TM)) were studied in detail. With a T(max) of 4 h and a terminal half-life of 33.6 days under fed conditions, lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least one month in cats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2966-6) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6044034 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60440342018-07-13 Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats Toutain, Céline E. Seewald, Wolfgang Jung, Martin Parasit Vectors Research BACKGROUND: Credelio(TM) (lotilaner) is an oral ectoparasiticide from the isoxazoline class developed for the treatment of flea and tick infestations in cats. It is formulated as a pure S-enantiomer in flavoured chewable tablets. The pharmacokinetics of lotilaner were investigated after intravenous or oral administration and under fed or fasted conditions in cats. Twenty-six adult cats were enrolled in a pharmacokinetic study evaluating either intravenous or oral administration of lotilaner. Following the oral administration at a dosage of 6 mg/kg, under fed or fasted conditions, or intravenous administration of 3 mg/kg, blood samples were collected up to 35 days after treatment. Lotilaner blood concentrations were measured using a validated liquid chromatography/tandem mass spectrometry method. Pharmacokinetic parameters were calculated by non-compartmental analysis. In addition, in vivo enantiomer stability of lotilaner was evaluated in a separate bioanalytical study. RESULTS: Following oral administration in fed cats, lotilaner was readily absorbed and peak blood concentrations reached within four hours. The terminal half-life was 33.6 days. Food enhanced the absorption, providing close to 100% oral bioavailability and reduced the inter-individual variability. Following intravenous administration, lotilaner had a low clearance of 0.13 l/kg/day, large volumes of distribution V(z) and V(ss) of 5.34 and 5.37 l/kg, respectively and a terminal half-life of 28.7 days. In addition, there was no in vivo racemization of lotilaner. CONCLUSIONS: The pharmacokinetic properties of lotilaner administered orally as a flavoured chewable tablet (Credelio(TM)) were studied in detail. With a T(max) of 4 h and a terminal half-life of 33.6 days under fed conditions, lotilaner provides a rapid onset of flea and tick killing activity with consistent and sustained efficacy for at least one month in cats. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13071-018-2966-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-13 /pmc/articles/PMC6044034/ /pubmed/30001724 http://dx.doi.org/10.1186/s13071-018-2966-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Toutain, Céline E. Seewald, Wolfgang Jung, Martin Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats |
title | Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats |
title_full | Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats |
title_fullStr | Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats |
title_full_unstemmed | Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats |
title_short | Pharmacokinetics of lotilaner following a single oral or intravenous administration in cats |
title_sort | pharmacokinetics of lotilaner following a single oral or intravenous administration in cats |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044034/ https://www.ncbi.nlm.nih.gov/pubmed/30001724 http://dx.doi.org/10.1186/s13071-018-2966-6 |
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