In:
Antiviral Therapy, SAGE Publications, Vol. 15, No. 7 ( 2010-10), p. 975-983
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1359-6535
,
2040-2058
Language:
English
Publisher:
SAGE Publications
Publication Date:
2010
detail.hit.zdb_id:
2118396-X
SSG:
15,3
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