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\begin{document}

\title{Cyclophosphamide pharmacogenomics and their effect on its bioactivation
and pharmacokinetics}



\author[1]{Ibrahim El-Serafi}%
\author[1]{Sinclair Steele}%
\affil[1]{Ajman University}%


\vspace{-1em}



  
  \date{May 28, 2024}


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\begin{abstract}
Cyclophosphamide (Cy) is a prodrug that is mainly bioactivated by the
cytochrome enzyme CYP2B6. Several other enzymes are also involved in its
bioactivation and affect its kinetics. Previous studies have shown the
effect of the enzymes' genetic polymorphisms on Cy kinetics and its
clinical outcome. These results were controversial primarily because of
the involvement of several interacting enzymes in the Cy metabolic
pathway, which can be also affected by several clinical factors as well
as other drugs interactions. In this article, we present the effect of
CYP2B6 polymorphisms on Cy kinetics since it is the main bioactivating
enzyme, as well as discussing all previously reported enzymes and
clinical factors that can alter Cy efficacy. Additionally, we present
explanations for key Cy side effects due to its extrahepatic
bioactivation. Finally, we discuss the role of busulphan in conditioning
regimens in the Cy metabolic pathway as a clinical example of drug-drug
interactions involving several enzymes. By the end of this article, our
aim is to have provided a conclusive summary of Cy pharmacogenomics and
the effect of its kinetics. The use of these findings in new strategies
for Cy personalized patient dose adjustment will certainly help in
optimizing the Cy dose and in improving the clinical outcome.%
\end{abstract}%



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