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]; AUCdextromethorphan/AUCdextrorphan) 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.
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