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Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time

Monitoring iohexol plasma clearance is considered a useful, reliable, and sensitive tool to establish glomerular filtration rate (GFR) and early stages of kidney disease in both humans and veterinary medicine. The assessment of GFR based on iohexol plasma clearance needs repeated blood sampling over...

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Autores principales: Baklouti, Sarah, Concordet, Didier, Borromeo, Vitaliano, Pocar, Paola, Scarpa, Paola, Cagnardi, Petra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116701/
https://www.ncbi.nlm.nih.gov/pubmed/33995036
http://dx.doi.org/10.3389/fphar.2021.634404
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author Baklouti, Sarah
Concordet, Didier
Borromeo, Vitaliano
Pocar, Paola
Scarpa, Paola
Cagnardi, Petra
author_facet Baklouti, Sarah
Concordet, Didier
Borromeo, Vitaliano
Pocar, Paola
Scarpa, Paola
Cagnardi, Petra
author_sort Baklouti, Sarah
collection PubMed
description Monitoring iohexol plasma clearance is considered a useful, reliable, and sensitive tool to establish glomerular filtration rate (GFR) and early stages of kidney disease in both humans and veterinary medicine. The assessment of GFR based on iohexol plasma clearance needs repeated blood sampling over hours, which is not easily attainable in a clinical setting. The study aimed to build a population pharmacokinetic (Pop PK) model to estimate iohexol plasma clearance in a population of dogs and based on this model, to indicate the best sampling times that enable a precise clearance estimation using a low number of samples. A Pop PK model was developed based on 5 iohexol plasma samples taken from 5 to 180 minutes (min) after an intravenous iohexol nominal dose of 64.7 mg/kg from 49 client-owned dogs of different breeds, sexes, ages, body weights, and clinical conditions (healthy or presenting chronic kidney disease CKD). The design of the best sampling times could contain either 1 or 2 or 3 sampling times. These were discretized with a step of 30 min between 30 and 180 min. A two-compartment Pop PK model best fitted the data; creatinine and kidney status were the covariates included in the model to explain a part of clearance variability. When 1 sample was available, 90 or 120 min were the best sampling times to assess clearance for healthy dogs with a low creatinine value. Whereas for dogs with CKD and medium creatinine value, the best sampling time was 150 or 180 min, for CKD dogs with a high creatinine value, it was 180 min. If 2 or 3 samples were available, several sampling times were possible. The method to define the best sampling times could be used with other Pop PK models as long as it is representative of the patient population and once the model is built, the use of individualized sampling times for each patient allows to precisely estimate the GFR.
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spelling pubmed-81167012021-05-14 Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time Baklouti, Sarah Concordet, Didier Borromeo, Vitaliano Pocar, Paola Scarpa, Paola Cagnardi, Petra Front Pharmacol Pharmacology Monitoring iohexol plasma clearance is considered a useful, reliable, and sensitive tool to establish glomerular filtration rate (GFR) and early stages of kidney disease in both humans and veterinary medicine. The assessment of GFR based on iohexol plasma clearance needs repeated blood sampling over hours, which is not easily attainable in a clinical setting. The study aimed to build a population pharmacokinetic (Pop PK) model to estimate iohexol plasma clearance in a population of dogs and based on this model, to indicate the best sampling times that enable a precise clearance estimation using a low number of samples. A Pop PK model was developed based on 5 iohexol plasma samples taken from 5 to 180 minutes (min) after an intravenous iohexol nominal dose of 64.7 mg/kg from 49 client-owned dogs of different breeds, sexes, ages, body weights, and clinical conditions (healthy or presenting chronic kidney disease CKD). The design of the best sampling times could contain either 1 or 2 or 3 sampling times. These were discretized with a step of 30 min between 30 and 180 min. A two-compartment Pop PK model best fitted the data; creatinine and kidney status were the covariates included in the model to explain a part of clearance variability. When 1 sample was available, 90 or 120 min were the best sampling times to assess clearance for healthy dogs with a low creatinine value. Whereas for dogs with CKD and medium creatinine value, the best sampling time was 150 or 180 min, for CKD dogs with a high creatinine value, it was 180 min. If 2 or 3 samples were available, several sampling times were possible. The method to define the best sampling times could be used with other Pop PK models as long as it is representative of the patient population and once the model is built, the use of individualized sampling times for each patient allows to precisely estimate the GFR. Frontiers Media S.A. 2021-04-29 /pmc/articles/PMC8116701/ /pubmed/33995036 http://dx.doi.org/10.3389/fphar.2021.634404 Text en Copyright © 2021 Baklouti, Concordet, Borromeo, Pocar, Scarpa and Cagnardi. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Baklouti, Sarah
Concordet, Didier
Borromeo, Vitaliano
Pocar, Paola
Scarpa, Paola
Cagnardi, Petra
Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time
title Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time
title_full Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time
title_fullStr Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time
title_full_unstemmed Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time
title_short Population Pharmacokinetic Model of Iohexol in Dogs to Estimate Glomerular Filtration Rate and Optimize Sampling Time
title_sort population pharmacokinetic model of iohexol in dogs to estimate glomerular filtration rate and optimize sampling time
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116701/
https://www.ncbi.nlm.nih.gov/pubmed/33995036
http://dx.doi.org/10.3389/fphar.2021.634404
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