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CYP3A induction and...
CYP3A induction and inhibition by different antiretroviral regimens reflected by changes in plasma 4beta-hydroxycholesterol levels
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Josephson, F. (author)
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- Bertilsson, L. (author)
- Karolinska Institutet
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- Bottiger, Y. (author)
- Karolinska Institutet
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- Flamholc, Leo (author)
- Lund University,Lunds universitet,Enheten för infektionssjukdomar,Forskargrupper vid Lunds universitet,Infectious Diseases Research Unit,Lund University Research Groups
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- Gisslén, Magnus, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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Ormaasen, V. (author)
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- Sönnerborg, A. (author)
- Karolinska Institutet
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- Diczfalusy, U. (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2008-05-06
- 2008
- English.
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In: European Journal of Clinical Pharmacology. - : Springer Science and Business Media LLC. - 0031-6970 .- 1432-1041. ; 64:8, s. 775-81
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Abstract
Subject headings
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- OBJECTIVE AND METHODS: A member of the major human cytochrome P450 superfamily of hemoproteins, CYP3A4/5, converts cholesterol into 4beta-hydroxycholesterol. We studied plasma 4beta-hydroxycholesterol levels prior to and 4 weeks after initiating antiretroviral therapy that included efavirenz, ritonavir-boosted atazanavir or ritonavir-boosted lopinavir with the aim of exploring the usefulness of plasma 4beta-hydroxycholesterol levels as an endogenous biomarker of CYP3A activity. Efavirenz is an inducer of CYP3A, whereas the ritonavir-boosted regimens are net inhibitors of CYP3A. RESULTS: In patients treated with efavirenz, the median plasma 4beta-hydroxycholesterol level increased by 46 ng/mL (p = 0.004; n = 11). In contrast, patients given ritonavir-boosted atazanavir showed a median decrease in plasma 4beta-hydroxycholesterol of -9.4 ng/mL (p = 0.0003; n = 22), and those given ritonavir-boosted lopinavir showed a median change from baseline of -5.8 ng/mL (p = 0.38; n = 19). There were significant between-group differences in the effects of antiretroviral treatment on plasma 4beta-hydroxycholesterol levels (p < 0.0001). CONCLUSION: Changes in plasma 4beta-hydroxycholesterol following the initiation of efavirenz- or atazanavir/ritonavir-based antiretroviral therapy reflected the respective net increase and decrease of CYP3A activity of these regimens. The plasma 4beta-hydroxycholesterol level did not indicate a net CYP3A inhibition in the lopinavir/ritonavir arm, possibly because of concomitant enzyme induction.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Keyword
- Adult
- Aged
- Anti-HIV Agents/*pharmacology
- Benzoxazines/pharmacology
- Cytochrome P-450 CYP3A/*drug effects/metabolism
- Drug Therapy
- Combination
- Enzyme Induction/drug effects
- Enzyme Inhibitors/pharmacology
- Female
- HIV Infections/drug therapy
- HIV Protease Inhibitors/*pharmacology
- Humans
- Hydroxycholesterols/blood/metabolism
- Male
- Middle Aged
- Oligopeptides/pharmacology
- Pyridines/pharmacology
- Pyrimidinones/pharmacology
- Ritonavir/pharmacology
- Young Adult
- 4 beta-hydroxycholesterol
- CYP3A
- antiretroviral
- biomarker
- inhibition
- induction
Publication and Content Type
- ref (subject category)
- art (subject category)
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