Summary of inhibition kinetics of UGT1A1 bilirubin glucuronidation by atazanavir and indinavira
where E = UGT; S = bilirubin; and I = BMS-232632 or indinavir.
HIV Inhibitor | Ki | αKi | Inhibition Mechanism | Predicted Inhibition at Csse |
|---|---|---|---|---|
| μM | % | |||
| Atazanavirb | 1.9 | 16.4 (α = 8.6) | Linear mixed | 28.7 |
| Indinavirc | 47.9 | 1317 (α = 27.5) | Linear mixedd | 2.5 |
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↵ a Human cDNA-expressed UGT1A1 in lymphoblast cells.
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↵ b UGT1A1: apparent Km = 4 μM and Vmax = 80 pmol/min mg protein in this set of experiments.
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↵ c UGT1A1: apparent Km = 2.8 μM and Vmax = 62 pmol/min mg protein in this set of experiments.
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↵ d A noncompetitive mechanism with a Ki = 100 μM was reported (Food and Drug Administration summary basis of approval, indinavir).
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↵ e For atazanavir, Css = 1.73 μM (400 mg q.i.d.); for indinavir, Css = 3.84 μM (Crixivan package insert, 800 mg t.i.d.); [bilirubin] = 6.84 μM.