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127418

PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME

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Last updated: 25 Dec 2024

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Abstract

Background: Down syndrome (DS); a common chromosomal abnormality in humans can affect multiple organ systems. DS individuals usually use a wide range of medications. There is a gap in knowledge about the extent of contribution of CYP3A4/5 in altered clinical response to medications in DS children.
Objectives: Phenotyping of CYP3A4/5 in DS children using. the ratio of 4β-hydroxycholesterol / Cholesterol (4β-OHC/C) as an endogenous biomarker for CYP3A4/5 activity.
Method: The study was an observational case control study, conducted in the DS clinic, King Abdul-Aziz University Hospital. Blood samples were taken for thyroid and liver function test by automated immunoassay procedure and analysis of cholesterol and 4β-hydroxycholesterol by gas chromatography.
Results: 16 DS and 29 non-DS children were enrolled (1-12 Y). Children with DS showed a lower median 4β-OHC/C molar ratio of 0.19×10-4 compared to 0.45×10-4 in the control group and with interquartile range (IQR) 0.17, 0.36 respectively (p < 0.001 Mann Whitney U test). DS children also showed an abnormality in liver enzymes and hypercholesteremia.
Conclusion: Children with DS had about two-fold lower CYP3A4/5 activity compared to children without DS. More studies to confirm these observations are required, however, drugs should be used cautiously in DS children.

DOI

10.21608/bfsa.2020.127418

Authors

First Name

Zoheir

Last Name

Damanhouri

MiddleName

A.

Affiliation

Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia

Email

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City

-

Orcid

-

First Name

Ahmed

Last Name

Ali

MiddleName

S.

Affiliation

Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia & Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt

Email

-

City

-

Orcid

-

First Name

Jumana

Last Name

AlAama

MiddleName

Y.

Affiliation

Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University (KAU), Saudi Arabia

Email

-

City

-

Orcid

-

First Name

Fuad

Last Name

Almaweri

MiddleName

Y.

Affiliation

Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia

Email

fuadalmaweri@hotmail.com

City

-

Orcid

-

First Name

Alaa

Last Name

Khedr

MiddleName

M.

Affiliation

Departmentt of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University (KAU), Saudi Arabia

Email

akhedr@kau.edu.sa

City

-

Orcid

-

First Name

Lateef

Last Name

Khan

MiddleName

M.

Affiliation

Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia

Email

lmkhan00@hotmail.com

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-

Orcid

-

Volume

43

Article Issue

2

Related Issue

19039

Issue Date

2020-12-01

Receive Date

2020-07-18

Publish Date

2020-12-01

Page Start

225

Page End

235

Print ISSN

1110-0052

Online ISSN

3009-7703

Article File

BFSA_Volume 43_Issue 2_Pages 225-235.pdf

PDF . 770.0kB

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https://bpsa.journals.ekb.eg/article_127418.html

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https://bpsa.journals.ekb.eg/service?article_code=127418

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13

Type

Original Article

Type Code

1,096

Publication Type

Journal

Publication Title

Bulletin of Pharmaceutical Sciences Assiut University

Publication Link

https://bpsa.journals.ekb.eg/

MainTitle

PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME

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Article

Created At

22 Jan 2023