Effects of CYP2D6*10, CYP3A5*3, CYP1A2*1F, and ABCB1 C3435T polymorphisms on the pharmacokinetics of flecainide in healthy Chinese subjects.
Drug Metabol Drug Interact
; 27(1): 33-9, 2012 Jan 09.
Article
in En
| MEDLINE
| ID: mdl-22718623
ABSTRACT
BACKGROUND:
Although flecainide is thought to be meta-bolized predominantly by cytochrome P450 (CYP) 2D6, it shows pharmacokinetic interactions with drugs, such as verapamil and digoxin, which may suggest other CYP pathways or ATP-binding cassette (ABC) transporters might be involved. This study evaluated effects of common polymorphisms in Chinese in CYP2D6, CYP3A5, CYP1A2, and ABCB1 on flecainide pharmacokinetics.METHODS:
Single oral 100-mg doses of flecainide were given to 15 healthy male Chinese subjects who were genotyped for the CYP2D6*2, *5, *10, CYP3A5*3, CYP1A2*1F and ABCB1 C1236T, G2677T/A, and C3435T polymorphisms.RESULTS:
There was no significant difference in the pharmacokinetics of flecainide among CYP2D6 (mainly involving *10) genotypes. The CYP3A5*3/*3 subjects (n=8) had a 26% higher systemic exposure (AUC0-∞) and 17% lower apparent oral clearance of flecainide than the combined group of CYP3A5*1/*1 (n=6) and CYP3A5*1/*3 (n=1) subjects (p<0.05). Subjects homozygous for CYP1A2*1F tended to have lower systemic exposure and increased clearance of flecainide compared to those with CYP1A2*1A/1F in subjects with at least one CYP2D6 variant allele.CONCLUSIONS:
The disposition of flecainide appeared to be influenced by the CYP3A5*3 and possibly the CYP1A2*1F polymorphisms, particularly in subjects with CYP2D6 variant alleles.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Flecainide
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Cytochrome P-450 CYP1A2
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Cytochrome P-450 CYP2D6
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Cytochrome P-450 CYP3A
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Anti-Arrhythmia Agents
Limits:
Adult
/
Humans
/
Male
Language:
En
Journal:
Drug Metabol Drug Interact
Journal subject:
FARMACOLOGIA
Year:
2012
Document type:
Article