Evaluation of felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions.
Eur J Clin Pharmacol
; 70(9): 1115-22, 2014 Sep.
Article
em En
| MEDLINE
| ID: mdl-25028073
ABSTRACT
OBJECTIVE:
To evaluate felodipine as a potential perpetrator of pharmacokinetic drug-drug interactions (PK-DDIs) involving cytochrome P450 (CYP) enzymes and P-glycoprotein (P-gp).METHODS:
Felodipine extended-release 10 mg was administered daily to six healthy subjects for 7 days (days 1-7). Subjects were administered a modified Inje cocktail comprising the selective probe substrates caffeine 100 mg (CYP1A2), losartan 25 mg (CYP2C9), omeprazole 20 mg (CYP2C19), dextromethorphan 30 mg (CYP2D6), midazolam 2 mg (CYP3A) and digoxin 250 µg (P-gp) on day 0 (prior to felodipine exposure) and day 7 (after felodipine exposure). Plasma samples were collected over 24 h and drug concentrations measured by UPLC-MS/MS.RESULTS:
The geometric means of the area under the plasma concentration-time curve ratios (probe AUC after felodipine exposure/probe AUC prior to felodipine exposure) and 95% confidence intervals for each probe were caffeine 0.91 (0.64-1.30), losartan 1.05 (0.95-1.15), omeprazole 1.17 (0.78-1.76), dextromethorphan 1.46 (1.00-2.12), midazolam 1.23 (0.99-1.52) and digoxin 1.01 (0.89-1.15).CONCLUSION:
Felodipine may be a weak in vivo inhibitor of CYP3A and CYP2D6 but is unlikely to act as a significant perpetrator of PK-DDIs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bloqueadores dos Canais de Cálcio
/
Felodipino
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Inibidores das Enzimas do Citocromo P-450
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Anti-Hipertensivos
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article