Compound Number | Species | Predicted Plasma Clearance,a CLP | Observed Plasma Clearance,b CLP | Observed/Predictedc | Corrected Predicted Human Plasma Clearance,d CLP | |
---|---|---|---|---|---|---|
ml/min/kg | ml/min/kg | |||||
1 | Rat | 9.8 | 30.3 ± 3.2 (9) | 3.1 | 4.8 | |
Dog | 1.6 | 7.3 ± 0.8 (8) | 4.6 | 7.3 | ||
Monkey | 7.3 | 20 ± 6 (2) | 2.7 | 4.3 | ||
Rabbit | 1.1 | 5.2 ± 0.3 (2) | 4.5 | 7.1 | ||
Human | 1.6 | |||||
2 (Raltegravir) | Rat | 11.9 | 38.3 ± 3.0 (7) | 3.2 | 3.4 | |
Dog | 0.9 | 5.4 ± 0.6 (5) | 5.9 | 6.3 | ||
Monkey | 5.6 | 18.6 ± 3.9 (3) | 3.3 | 3.5 | ||
Rabbit | 1.3 | 8.2 ± 1.0 (3) | 6.1 | 6.6 | ||
Human | 1.1 | |||||
3 | Rat | 2.3 | 5.4 ± 2.5 (3) | 2.4 | 2.3 | |
Dog | 1.9 | 7.5 ± 1.2 (3) | 4.0 | 3.9 | ||
Monkey | 3.6 | 8.9 ± 1.0 (3) | 2.5 | 2.4 | ||
Rabbit | 5.2 | 9.5 ± 1.4 (3) | 1.8 | 1.8 | ||
Human | 1.0 | |||||
4 | Rat | 2.4 | 6.5 ± 1.1 (3) | 2.7 | 7.6 | |
Dog | 1.5 | 4.8 ± 0.7 (3) | 3.2 | 8.9 | ||
Monkey | 10.6 | 20 ± 4 (2) | 1.9 | 5.3 | ||
Rabbit | 2.8 | 4.2 ± 0.5 (3) | 1.4 | 4.0 | ||
Human | 2.8 | |||||
5 | Rat | 1.1 | 1.7 ± 0.3 (3) | 1.5 | 4.7 | |
Dog | 0.6 | 1.8 ± 0.3 (3) | 3.1 | 9.6 | ||
Monkey | 11.3 | 17.9 ± 2.7 (2) | 1.6 | 4.9 | ||
Rabbit | 4.9 | 7.3 ± 1.0 (3) | 1.4 | 4.3 | ||
Human | 3.1 | |||||
6 | Rat | 0.4 | 2.3 ± 0.4 (3) | 6.1 | 1.6 | |
Dog | 0.4 | 3.1 ± 0.1 (3) | 7.4 | 1.9 | ||
Rabbit | 0.4 | 2.2 ± 0.3 (3) | 5.5 | 1.4 | ||
Human | 0.3 | |||||
7 | Rat | 2.7 | 1.8 ± 0.1 (3) | 0.7 | 3.7 | |
Dog | 5.6 | 3.8 ± 0.6 (3) | 0.7 | 3.7 | ||
Monkey | 21.3 | 26.5 ± 2.5 (3) | 1.2 | 6.9 | ||
Human | 5.5 | |||||
8 | Rat | 9.7 | 16.5 ± 2.4 (4) | 1.1 | 0.3 | |
Dog | 0.3 | 1.8 ± 0.1 (4) | 3.9 | 0.9 | ||
Monkey | 3.5 | 15.2 ± 0.1 (2) | 2.8 | 0.7 | ||
Human | 0.2 | |||||
9 | Rat | 4.4 | 14.3 ± 0.7 (3) | 3.2 | 0.7 | |
Dog | 1.1 | 9.3 ± 0.4 (2) | 8.3 | 1.8 | ||
Monkey | 8.0 | 16.5 ± 2.5 (3) | 2.1 | 0.4 | ||
Human | 0.2 | |||||
10 | Rat | 0.3 | 2.4 ± 0.7 (3) | 7.2 | 10.8 | |
Dog | 0.7 | 3.4 ± 0.2 (3) | 4.5 | 6.8 | ||
Monkey | 10.8 | 22.5 ± 5.5 (3) | 2.1 | 3.1 | ||
| Human | 1.5 |
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↵ a Predicted plasma clearance scaled from in vitro data according to eqs. 3 and 4.
↵ b Values of observed plasma clearance are the mean ± S.E. of the number of experiments shown in parentheses.
↵ c Ratio between observed and predicted plasma clearance.
↵ d Corrected predicted human CLP was calculated by multiplying predicted human CLP by O/P for each preclinical animal species. For example, predicted human CLP for compound 1 is 1.56 ml/min/kg. O/P for rat is 3.09. Thus, corrected predicted human CLP based on rat data is 4.8 ml/min/kg. Apparent discrepancies in products or ratios are due to rounding.