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The effect of atorv...
The effect of atorvastatin treatment on serum oxysterol concentrations and cytochrome P450 3A4 activity
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- Hukkanen, J. (författare)
- University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland
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- Puurunen, J. (författare)
- University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland
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- Hyötyläinen, Tuulia, 1971- (författare)
- Steno Diabetes Center, Gentofte, Denmark
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- Savolainen, M. J. (författare)
- University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland
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- Ruokonen, A. (författare)
- University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland
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- Morin-Papunen, L. (författare)
- University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland
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- Oresic, Matej, 1967- (författare)
- Steno Diabetes Center, Gentofte, Denmark
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- Piltonen, T. (författare)
- University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland
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- Tapanainen, J. S. (författare)
- University of Oulu, Oulu, Finland; Oulu University Hospital, Oulu, Finland; University of Helsinki, Helsinki, Finland; Helsinki University Hospital, Helsinki, Finland
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(creator_code:org_t)
- 2015-07-22
- 2015
- Engelska.
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Ingår i: British Journal of Clinical Pharmacology. - : Blackwell Publishing. - 0306-5251 .- 1365-2125. ; 80:3, s. 473-479
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aims: Atorvastatin is known to both inhibit and induce the cytochrome P450 3A4 (CYP3A4) enzyme in vitro. Some clinical studies indicate that atorvastatin inhibits CYP3A4 but there are no well-controlled longer term studies that could evaluate the inducing effect of atorvastatin. We aimed to determine if atorvastatin induces or inhibits CYP3A4 activity as measured by the 4β-hydroxycholesterol to cholesterol ratio (4βHC : C).Methods: In this randomized, double-blind, placebo-controlled 6 month study we evaluated the effects of atorvastatin 20mg day1 (n=15) and placebo (n = 14) on oxysterol concentrations and determined if atorvastatin induces or inhibits CYP3A4 activity as assessed by the 4βHC : C index. The respective 25-hydroxycholesterol and 5α,6α- epoxycholesterol ratios were used as negative controls.Results: Treatment with atorvastatin decreased 4βHC and 5α,6α-epoxycholesterol concentrations by 40% and 23%, respectively. The mean 4βHC : C ratio decreased by 13% (0.214 ± 0.04 to 0.182 ± 0.04, P = 0.024, 95% confidence interval (CI) of the difference –0.0595, –0.00483) in the atorvastatin group while no significant change occurred in the placebo group. The difference in change of 4βHC : C between study arms was statistically significant (atorvastatin –0.032, placebo 0.0055, P = 0.020, 95% CI of the difference – 0.069, –0.0067). The ratios of 25-hydroxycholesterol and 5α,6α- epoxycholesterol to cholesterol did not change.Conclusions: The results establish atorvastatin as an inhibitor of CYP3A4 activity.Furthermore, 4βHC : C is a useful index of CYP3A4 activity, including theconditions with altered cholesterol concentrations.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- 25-hydroxycholesterol
- 4β-hydroxycholesterol
- 5α
- 6α-epoxycholesterol
- atorvastatin
- desmosterol
- pregnane X receptor
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Hukkanen, J.
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Puurunen, J.
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Hyötyläinen, Tuu ...
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Savolainen, M. J ...
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Ruokonen, A.
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Morin-Papunen, L ...
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Oresic, Matej, 1 ...
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Piltonen, T.
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Tapanainen, J. S ...
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