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Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People

Trimethoprim‐sulfamethoxazole (TMP‐SMX) is one of the most widely drugs on earth. The World Health Organization recommends it as an essential basic drug for all healthcare systems. Dosing is inconsistently based on weight, assuming linear relationships. Given that obesity is now a global “pandemic”...

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Autores principales: Hall, RG, Pasipanodya, JG, Meek, C, Leff, RD, Swancutt, M, Gumbo, T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193002/
https://www.ncbi.nlm.nih.gov/pubmed/27869362
http://dx.doi.org/10.1002/psp4.12146
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author Hall, RG
Pasipanodya, JG
Meek, C
Leff, RD
Swancutt, M
Gumbo, T
author_facet Hall, RG
Pasipanodya, JG
Meek, C
Leff, RD
Swancutt, M
Gumbo, T
author_sort Hall, RG
collection PubMed
description Trimethoprim‐sulfamethoxazole (TMP‐SMX) is one of the most widely drugs on earth. The World Health Organization recommends it as an essential basic drug for all healthcare systems. Dosing is inconsistently based on weight, assuming linear relationships. Given that obesity is now a global “pandemic” it is vital that we evaluate the effect of obesity on trimethoprim‐sulfamethoxazole concentrations. We conducted a prospective clinical experiment based on optimized design strategies and artificial intelligence algorithms and found that weight and body mass index (BMI) had a profound effect on drug clearance and volume of distribution, and followed nonlinear fractal geometry‐based relationships. The findings were confirmed by demonstrating decreased TMP‐SMX peak and area under the concentration‐time curves in overweight patients based on standard regression statistics. The nonlinear relationships can now be used to identify new TMP‐SMX doses in overweight and obese patients for each of the infections caused by the >60 pathogens for which the drug is indicated.
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spelling pubmed-51930022016-12-29 Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People Hall, RG Pasipanodya, JG Meek, C Leff, RD Swancutt, M Gumbo, T CPT Pharmacometrics Syst Pharmacol Original Articles Trimethoprim‐sulfamethoxazole (TMP‐SMX) is one of the most widely drugs on earth. The World Health Organization recommends it as an essential basic drug for all healthcare systems. Dosing is inconsistently based on weight, assuming linear relationships. Given that obesity is now a global “pandemic” it is vital that we evaluate the effect of obesity on trimethoprim‐sulfamethoxazole concentrations. We conducted a prospective clinical experiment based on optimized design strategies and artificial intelligence algorithms and found that weight and body mass index (BMI) had a profound effect on drug clearance and volume of distribution, and followed nonlinear fractal geometry‐based relationships. The findings were confirmed by demonstrating decreased TMP‐SMX peak and area under the concentration‐time curves in overweight patients based on standard regression statistics. The nonlinear relationships can now be used to identify new TMP‐SMX doses in overweight and obese patients for each of the infections caused by the >60 pathogens for which the drug is indicated. John Wiley and Sons Inc. 2016-11-21 2016-12 /pmc/articles/PMC5193002/ /pubmed/27869362 http://dx.doi.org/10.1002/psp4.12146 Text en © 2016 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Hall, RG
Pasipanodya, JG
Meek, C
Leff, RD
Swancutt, M
Gumbo, T
Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People
title Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People
title_full Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People
title_fullStr Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People
title_full_unstemmed Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People
title_short Fractal Geometry‐Based Decrease in Trimethoprim‐Sulfamethoxazole Concentrations in Overweight and Obese People
title_sort fractal geometry‐based decrease in trimethoprim‐sulfamethoxazole concentrations in overweight and obese people
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193002/
https://www.ncbi.nlm.nih.gov/pubmed/27869362
http://dx.doi.org/10.1002/psp4.12146
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