\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[english]{babel}



\usepackage{float}








\begin{document}

\title{Physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD)
modeling as a tool for antiviral drug dose regimens for COVID-19}



\author[1]{Teerachat Saeheng}%
\author[1]{Juntra Karbwang}%
\author[2]{Kesara Na-Bangchang}%
\affil[1]{Thammasat University - Rangsit Campus}%
\affil[2]{Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College, Thammasat University}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background and Purpose: Ritonavir-boosted lopinavir and chloroquine were
withdrawn for COVID-19 treatment according to WHO recommendation.
However, lopinavir is still being used for COVID-19 treatment in a
clinical practice guideline without supportive evidence. We demonstrated
the utility of physiologically-based pharmacokinetic
(PBPK)/pharmacodynamic (PD) models to support clinical use of lopinavir
and the withdrawal of chloroquine for COVID-19 treatment. Experimental
approach: The developed whole-body PBPK models were validated against
clinical data. Model validation was performed using acceptable methods.
The inhibitory effect (\%E) was calculated to demonstrate drug efficacy.
The recommended drug regimen for COVID-19 was the combination of 400/100
mg lopinavir/ritonavir given twice daily and 300 mg base chloroquine
given twice daily for 14 days. Key Results: This study successfully
developed whole-body PBPK models (AAFEs of 1.2-fold). For patients with
a 70 kg body weight, \%E for chloroquine in epithelial lining fluid
(ELF) and bronchial epithelial cells (BEC) were about 2\% and 12\%,
respectively. The corresponding values for lopinavir were 66\% and
87.4\%, respectively. With the increased body weight to 90 kg, \%E for
lopinavir in BEC dramatically dropped to lower than 60\%, while that in
ELF was slightly decreased (86.87\%). Conclusion and Implications: The
results support the decision of withdrawing chloroquine and using
lopinavir in asymptomatic (with positive antigen kit test) or mild
COVID-19 cases. In addition, results support the administration of
antiviral drugs within the ten days of infection to prevent treatment
failure.%
\end{abstract}%



\sloppy


\textbf{Hosted file}

\verb`[PBPK COVID-19][BJP][Maintext].docx`  available at \url{https://authorea.com/users/300409/articles/712183-physiologically-based-pharmacokinetic-and-pharmacodynamic-pbpk-pd-modeling-as-a-tool-for-antiviral-drug-dose-regimens-for-covid-19}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Table [BJP] [TS].docx`  available at \url{https://authorea.com/users/300409/articles/712183-physiologically-based-pharmacokinetic-and-pharmacodynamic-pbpk-pd-modeling-as-a-tool-for-antiviral-drug-dose-regimens-for-covid-19}

\selectlanguage{english}
\FloatBarrier
\end{document}

