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Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers by R AARNOUTSE; J KLEINNIJENHUIS; P KOOPMANS; D TOUW; J WIELING; Y HEKSTER; D BURGER is a Medicine article available to read on EtoBox.
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Effect of low-dose ritonavir (100 mg twice daily) on the activity of cytochrome P450 2D6 in healthy volunteers Objective: In the treatment of human immunodeficiency virus infection, the protease inhibitor ritonavir is used in a low dose (100 mg twice daily) to inhibit cytochrome P450 (CYP) 3A4 and thereby increase plasma concentrations of coadministered protease inhibitors. When applied in a therapeutic dose (600 mg twice daily), ritonavir also inhibits CYP2D6. The effect of low-dose ritonavir on CYP2D6 is unknown and was investigated in this study. Methods: This was a 1-arm, 2-period, fixed-order study in 13 healthy male volunteers who were extensive metabolizers of CYP2D6. The first period examined baseline CYP2D6 activity by evaluating the pharmacokinetics of a single dose of desipramine and by metabolic phenotyping with dextromethorphan. During the second period, participants took ritonavir, 100 mg twice daily, for 2 weeks, followed by repeat assessment of desipramine pharmacokinetics and the dextromethorphan metabolic phenotype in the presence of ritonavir. Results: Low-dose ritonavir (100 mg twice daily) significantly increased the exposure to single-dose desipramine, as refl
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- Author
- R AARNOUTSE; J KLEINNIJENHUIS; P KOOPMANS; D TOUW; J WIELING; Y HEKSTER; D BURGER
- Publisher
- Nature Publishing Group; Wiley (Blackwell Publishing); Wiley-Blackwell; Wiley; Springer Science and Business Media LLC; Research Square (ISSN 0009-9236)
- Published
- 2005
- Language
- EN
- Field
- Medicine (Health Sciences)