Figure 5.

Pre–steady-state kinetics of inhibition of cytochome P450 3A4-catalyzed 6β-hydroxylation of testosterone. Plots of product formation are shown: A, no inhibitor added (●), 0.4 μM ritonavir (▪), and 1.2 μM ritonavir (▲). B, no inhibitor added (●, same plot as in part A), 1.5 μM indinavir (▪), and 4 μM ritonavir (▲). The data points for the uninhibited reaction were fit by linear regression. The data points for the inhibitors in parts A and B could be fit to the expression y = A (1 − e^−k₁^t) + k_sst: A, k₁ = 0.062 s⁻¹ (t_1/2 11 s) and k_ss = 0.086⁻¹ (28% of uninhibited rate) for 1.2 μM ritonavir; B, k₁ = 0.17 s⁻¹ (t_1/2 4.0 s) and k_ss = 0.13 s⁻¹ (42% of uninhibited rate) for 1.2 μM ritonavir.