Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-38657
Jetter, A; Fätkenheuer, G; Frank, D; Klaassen, T; Seeringer, A; Doroshyenko, O; Kirchheiner, J; Hein, W; Schömig, E; Fuhr, U; Wyen, C (2010). Do activities of cytochrome P450 (CYP)3A, CYP2D6 and P-glycoprotein differ between healthy volunteers and HIV-infected patients? Antiviral Therapy, 15(7):975-983.
BACKGROUND: In inflammation and infection, cytochrome P450 (CYP) enzyme activities are down-regulated. Information on possible discrepancies in activities of CYP enzymes and drug transporters between HIV-infected patients and healthy people is limited. METHODS: We used midazolam, dextromethorphan and digoxin as in vivo phenotyping probes for CYP3A (CYP3A4/5), CYP2D6 and P-glycoprotein activities, respectively, and compared these activities between 12 healthy Caucasian volunteers and 30 treatment-naive HIV-infected patients. RESULTS: Among the HIV-infected patients, the overall CYP3A activity (apparent oral midazolam clearance) was approximately 50% of the activity observed in healthy volunteers (point estimate 0.490, 90% confidence interval [CI] 0.377-0.638). The CYP2D6 activity (plasma ratio area under the curve [AUC]; AUC(dextromethorphan)/AUC(dextrorphan)) was essentially unchanged (point estimate 1.289, 90% CI 0.778-2.136). P-glycoprotein activity was slightly lower in patients (digoxin maximum concentration point estimate 1.304, 90% CI 1.034-1.644). CONCLUSIONS: The overall CYP3A activity was approximately 50% lower in HIV-infected patients than in healthy volunteers. The CYP2D6 activity was highly variable, but, on average was not different between groups, whereas a marginally lower P-glycoprotein activity was observed in treatment-naive HIV-infected patients.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Clinical Pharmacology and Toxicology|
|DDC:||610 Medicine & health|
|Deposited On:||18 Jan 2011 12:44|
|Last Modified:||23 Nov 2012 16:12|
|Publisher:||International Medical Press|
|Additional Information:||This is the author’s version of a work accepted for publication by International Medical Press. Changes resulting from the publishing process, including peer review, editing and formatting, might not be reflected in this document. A definitive version was published in Antiviral Therapy, 2010, 15(7) © 2010 International Medical Press|
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