PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME
Damanhouri, Z., Ali, A., AlAama, J., Almaweri, F., Khedr, A., Khan, L. (2020). PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME. EKB Journal Management System, 43(2), 225-235. doi: 10.21608/bfsa.2020.127418
Zoheir A. Damanhouri; Ahmed S. Ali; Jumana Y. AlAama; Fuad Y. Almaweri; Alaa M. Khedr; Lateef M. Khan. "PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME". EKB Journal Management System, 43, 2, 2020, 225-235. doi: 10.21608/bfsa.2020.127418
Damanhouri, Z., Ali, A., AlAama, J., Almaweri, F., Khedr, A., Khan, L. (2020). 'PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME', EKB Journal Management System, 43(2), pp. 225-235. doi: 10.21608/bfsa.2020.127418
Damanhouri, Z., Ali, A., AlAama, J., Almaweri, F., Khedr, A., Khan, L. PHENOTYPING CYP3A4/5 USING AN ENDOGENOUS BIOMARKER IN CHILDREN WITH DOWN SYNDROME. EKB Journal Management System, 2020; 43(2): 225-235. doi: 10.21608/bfsa.2020.127418

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

Bulletin of Pharmaceutical Sciences Assiut University
Article 13, Volume 43, Issue 2, December 2020, Page 225-235  XML PDF (751.95 K)
Document Type: Original Article
DOI: 10.21608/bfsa.2020.127418
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Authors
Zoheir A. Damanhouri1; Ahmed S. Ali2; Jumana Y. AlAama3; Fuad Y. Almaweri1; Alaa M. Khedr4; Lateef M. Khan1
1Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia
2Department of Pharmacology, Faculty of Medicine, King Abdulaziz University (KAU), Saudi Arabia & Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt
3Princess Al-Jawhara Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University (KAU), Saudi Arabia
4Departmentt of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University (KAU), Saudi Arabia
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.
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