High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs.
Toxicol Appl Pharmacol
; 266(3): 452-8, 2013 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-23200775
ABSTRACT
It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P(450) enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient-drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin-Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV+αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV+αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV+αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirroles
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Alfa-Tocoferol
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Citocromo P-450 CYP3A
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Ácidos Heptanoicos
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Hígado
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Anticolesterolemiantes
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2013
Tipo del documento:
Article
País de afiliación:
Alemania
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
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USA