TABLE 1.
Total tissue concentrations, unbound fraction, and calculated tissue-to-medium or -perfusate partition coefficients (Kp and Kpu,u)
| Outcome | Ritonavir | Rosuvastatin | Furamidine | |||
|---|---|---|---|---|---|---|
| IPL | SCH | IPL | SCH | IPL | SCH | |
| Ctissue (μM) | 56 | 15 ± 2 | 18 | 17 ± 3 | 24c | 1500 ± 500 |
| Cmedium (μM) | 0.49 | 0.47 ± 0.12 | 0.54 | 1 | 0.0032c,d | 0.27 ± 0.19 |
| Kpobserved | 110 | 33 | 33 | 17 | 8400c,d | 6900 |
| Whole lysatea | ||||||
| fu,lysate (%) | 1.0 ± 0.1 | 3.0 ± 1.0 | 23 ± 1 | >36 ± 3b | 0.3 ± 0.1c | 0.9 ± 0.2 |
| Kppredicted | 100 | 35 | 4.3 | <2.8 | 330 | 110 |
| Cu,tissue (μM) | 0.56 | 0.46 ± 0.16 | 4.1 | >6.1 | 0.073 | 14 ± 6 |
| Kpu,u | 1.1 | 1.1 | 7.9 | >6.1 | 23 | 53 |
| Cytosola | ||||||
| fcytosol (%) | 36 | 43 ± 8 | 72 | 88 ± 1 | 20 | 3 ± 1 |
| fu,cytosol (%) | 3.3 ± 0.2 | 11 ± 1 | 46 ± 8 | >34 ± 3b | 6.2 ± 1.2c | 11 ± 4 |
| Kppredicted | 91 | 22 | 3.3 | <3.4 | 81 | 330 |
| Cu,tissue (μM) | 0.62 | 0.76 ± 0.31 | 5.9 | >5.0 | 0.30 | 4.3 ± 1.6 |
| Kpu,u | 1.3 | 1.7 | 11 | >5.0 | 93 | 16 |
a
Kppredicted and Cu,tissue calculated for lysate and cytosol as described in Materials and Methods.
b
Undiluted fu and subsequent calculations represented by inequalities when fu,measured > 80%, as described in Materials and Methods.
c
From Yan et al., 2011.
d
Taking into account fu of 44% in perfusate, containing 20% whole blood, as determined by Yan et al., 2011.