Effect of 95% Ethanol Khat Extract and Cathinone on in vitro Human Recombinant Cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 Activity.
Alkaloids
/ pharmacology
Catha
/ chemistry
Cytochrome P-450 CYP2C9
/ metabolism
Cytochrome P-450 CYP2C9 Inhibitors
/ pharmacology
Cytochrome P-450 CYP2D6
/ metabolism
Cytochrome P-450 CYP2D6 Inhibitors
/ pharmacology
Cytochrome P-450 CYP3A
/ metabolism
Cytochrome P-450 CYP3A Inhibitors
/ pharmacology
Drug Interactions
Ethanol
/ chemistry
Humans
Plant Extracts
/ pharmacology
Recombinant Proteins
/ metabolism
Solvents
/ chemistry
Journal
European journal of drug metabolism and pharmacokinetics
ISSN: 2107-0180
Titre abrégé: Eur J Drug Metab Pharmacokinet
Pays: France
ID NLM: 7608491
Informations de publication
Date de publication:
Jun 2019
Jun 2019
Historique:
pubmed:
12
10
2018
medline:
13
11
2019
entrez:
12
10
2018
Statut:
ppublish
Résumé
A significant number of people worldwide consume khat on daily basis. Long term of khat chewing has shown negative impact on several organ systems. It is likely that these people are co-administered khat preparations and conventional medication, which may lead to khat-drug interactions. This study aimed to reveal the inhibitory potencies of khat ethanol extract (KEE) and its major active ingredient (cathinone) on human cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 enzymes activities, which are collectively responsible for metabolizing 70-80% clinically used drugs. In vitro fluorescence-based enzyme assays were developed and the CYP enzyme activities were quantified in the presence and absence of KEE and cathinone employing Vivid KEE inhibited human CYP2C9, CYP2D6, and CYP3A4 enzyme activities with IC Khat-drug interactions are possible due to administration of clinical drugs metabolized by CYP2C9/CYP2D6/CYP3A4 together with khat chewing. Further in vivo studies are required to confirm our findings and identify the causative constituents of these inhibitory effects.
Sections du résumé
BACKGROUND AND OBJECTIVE
OBJECTIVE
A significant number of people worldwide consume khat on daily basis. Long term of khat chewing has shown negative impact on several organ systems. It is likely that these people are co-administered khat preparations and conventional medication, which may lead to khat-drug interactions. This study aimed to reveal the inhibitory potencies of khat ethanol extract (KEE) and its major active ingredient (cathinone) on human cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 enzymes activities, which are collectively responsible for metabolizing 70-80% clinically used drugs.
METHODS
METHODS
In vitro fluorescence-based enzyme assays were developed and the CYP enzyme activities were quantified in the presence and absence of KEE and cathinone employing Vivid
RESULTS
RESULTS
KEE inhibited human CYP2C9, CYP2D6, and CYP3A4 enzyme activities with IC
CONCLUSION
CONCLUSIONS
Khat-drug interactions are possible due to administration of clinical drugs metabolized by CYP2C9/CYP2D6/CYP3A4 together with khat chewing. Further in vivo studies are required to confirm our findings and identify the causative constituents of these inhibitory effects.
Identifiants
pubmed: 30306496
doi: 10.1007/s13318-018-0518-2
pii: 10.1007/s13318-018-0518-2
doi:
Substances chimiques
Alkaloids
0
Cytochrome P-450 CYP2C9 Inhibitors
0
Cytochrome P-450 CYP2D6 Inhibitors
0
Cytochrome P-450 CYP3A Inhibitors
0
Plant Extracts
0
Recombinant Proteins
0
Solvents
0
Ethanol
3K9958V90M
cathinone
540EI4406J
CYP2C9 protein, human
EC 1.14.13.-
Cytochrome P-450 CYP2C9
EC 1.14.13.-
Cytochrome P-450 CYP2D6
EC 1.14.14.1
Cytochrome P-450 CYP3A
EC 1.14.14.1
CYP3A4 protein, human
EC 1.14.14.55
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
423-431Subventions
Organisme : the University of Nottingham Malaysia Campus final year project grant
ID : BMS/FYP/2017-06
Organisme : the University of Nottingham Malaysia Campus final year project grant
ID : BMS-PY5
Organisme : University of Malaya, Malaysia
ID : RG539-13HTM
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