Excellent agreement between the observed and predicted magnitude of inhibition by rifampin of the in vivo rosuvastatin sinusoidal uptake clearance in the rat as measured by PET imaging
| Sinusoidal Uptake Clearance | ||
|---|---|---|
| Observeda | Predictedb | |
| ml/min per kg body weight | ||
| Rifampin (−) | 70.95 ± 2.88 | 80.44 ± 13.05 |
| Rifampin (+) | 37.28 ± 1.48 | 45.69 ± 7.95 |
| % Rifampin (−) | 52.5% | 56.8% |
↵a Observed data are from our previous positron emission tomography (PET) imaging study where the mean unbound concentration of rifampin after administration (40 mg/kg intravenous bolus plus 1.85 mg/min per kilogram intravenous infusion) was 9.4 µM (He et al., 2014).
↵b The in vivo predicted sinusoidal uptake clearance in the absence of rifampin was estimated by Michaelis-Menten constant (Km), maximum velocity of the uptake (Vmax), and diffusion rate constant (Kd) (Table 1) and the abundance of organic anion transporting polypeptide (Oatp) protein as reported previously (Ishida et al., 2018). The in vivo predicted sinusoidal uptake clearance in the presence of rifampin was calculated by eq. 2, and the % remaining activity of each Oatp in the presence of 9.4 µM rifampin (94.8%, 10.5%, and 18.9% for Oatp1a1, 1a4, and 1b2, respectively) was obtained from Fig. 4, A–C.