Michaelis-Menten parameters (Km, Km × fu, Vmax) describing atazanavir metabolism in RLM and SRH, together with corresponding total and unbound intrinsic clearance values (Clint and Clint/fu)
Km and Vmax values were obtained by fitting the Michaelis-Menten equation to the observed rate of metabolic atazanavir disappearance as a function of the atazanavir concentration (Fig. 2). Values are means ± S.D. of triplicate experiments with two batches of SRH and two batches of RLM.
| Metabolism Parameter | Model System | ||
|---|---|---|---|
| Fresh SRH | Cryo SRH | RLM | |
| Km (μM) | 0.86 ± 0.13 | 1.22 ± 0.19 | 0.35 ± 0.04 |
| Km × fu (μM) | 0.83 ± 0.14 | 0.94 ± 0.24 | 0.26 ± 0.04 |
| Kpu,u (ratio of unbound intra- to extracellular concentration) | 0.32 ± 0.07 | 0.28 ± 0.09 | — |
| Vmax (pmol/min per million cells or milligrams of protein) | 136 ± 6a | 122 ± 6a | 506 ± 17b |
| Clint (μl/min per million cells or milligrams of protein) | 158 ± 24c | 100 ± 16c | 1446 ± 175d |
| Clint/fu (μl/min million cells or milligrams of proteind) | 165 ± 28c | 129 ± 34c | 1910 ± 323d |
| Clint/(fu × Kpu,u) (μl/min per million cells) | 514 ± 149 | 459 ± 185 | 554 ± 105e |
↵a pmol/min per million cells.
↵b pmol/min per milligrams of protein.
↵c μl/min per million cells.
↵d μl/min per milligrams of protein.
↵e Clint,mic,u was recalculated to match the unit of μl/min per million cells, using the activity-based scaling factor (MPPMC, 0.30 mg of microsomal protein/million cells) previously determined with verapamil. No Kpu,u-correction was applied here (Nicolaï et al., 2015).