Compound Number | Species | Intrinsic Oxidative Clearance,a CLin_invitro | Intrinsic Glucuronidation Clearance,b CLin_invitro | Unbound Fraction in Plasma,cfu | Calculated Blood/Plasma Partition Ratio,d BP | Experimental Blood/Plasma Partition Ratio,e BP | |
---|---|---|---|---|---|---|---|
μl/min/mg microsomal protein | |||||||
1 | Rat | <1 | 20.3 ± 1.5 | 0.35 | 0.70 | 0.59 ± 0.06 | |
Dog | <1 | 2.9 ± 0.2 | 0.38 | 0.74 | 0.98 ± 0.09 | ||
Monkey | <1 | 39 ± 2 | 0.19 | 0.67 | 0.60 ± 0.10 | ||
Rabbit | <1 | 7.7 ± 0.8 | 0.11 | 0.68 | 0.80 ± 0.10 | ||
Human | <1 | 7.7 ± 0.6 | 0.28 | 0.68 | 0.62 ± 0.02 | ||
2 (Raltegravir) | Rat | <1 | 32 ± 2 | 0.27 | 0.66 | 0.71 ± 0.06 | |
Dog | <1 | 2.2 ± 0.3 | 0.29 | 0.70 | 0.87 ± 0.11 | ||
Monkey | <1 | 33 ± 2 | 0.15 | 0.65 | 0.80 ± 0.10 | ||
Rabbit | <1 | 10 ± 1 | 0.10 | 0.68 | 0.80 ± 0.10 | ||
Human | <1 | 8.3 ± 0.5 | 0.17 | 0.63 | 0.62 ± 0.10 | ||
3 | Rat | 12 ± 0.2 | 10.4 ± 1.7 | 0.06 | 0.57 | 0.65 ± 0.09 | |
Dog | 1.2 ± 0.2 | 4.3 ± 1.9 | 0.25 | 0.69 | 0.59 ± 0.05 | ||
Monkey | 10.4 ± 4.2 | 15.2 ± 0.9 | 0.12 | 0.64 | 0.60 ± 0.09 | ||
Rabbit | 4.7 ± 2.1 | 24 ± 8 | 0.16 | 0.70 | 0.60 ± 0.11 | ||
Human | 1.3 ± 0.6 | 5.4 ± 0.8 | 0.19 | 0.64 | 0.68 ± 0.03 | ||
4 | Rat | 10 ± 2.5 | 24.8 ± 2.9 | 0.04 | 0.56 | N.D. | |
Dog | 7 ± 2.0 | 3.2 ± 1.7 | 0.11 | 0.62 | N.D. | ||
Monkey | 14.0 ± 0.1 | 57 ± 22 | 0.17 | 0.66 | N.D. | ||
Rabbit | 4.4 ± 0.2 | 27.0 ± 3 | 0.07 | 0.67 | N.D. | ||
Human | 5.1 ± 0.6 | 19.3 ± 2.0 | 0.18 | 0.64 | N.D. | ||
5 | Rat | 23.8 ± 1.9 | 56.4 ± 6.6 | 0.008 | 0.54 | N.D. | |
Dog | 3.3 ± 2.3 | 11.4 ± 3.1 | 0.027 | 0.59 | N.D. | ||
Monkey | 34.2 ± 0.9 | 162 ± 7 | 0.073 | 0.62 | N.D. | ||
Rabbit | 13.0 ± 2 | 54 ± 4 | 0.063 | 0.66 | N.D. | ||
Human | 11.5 ± 0.1 | 44.7 ± 1.6 | 0.088 | 0.60 | N.D. | ||
6 | Rat | 7 ± 0.8 | 4.9 ± 0.3 | 0.016 | 0.55 | 0.70 ± 0.10 | |
Dog | 1.9 ± 0.2 | 1.5 ± 0.6 | 0.086 | 0.62 | 0.60 ± 0.06 | ||
Rabbit | 2.7 ± 0.4 | 3.7 ± 0.5 | 0.037 | 0.65 | N.D. | ||
Human | 2.3 ± 0.6 | 2.4 ± 0.2 | 0.067 | 0.59 | 0.50 ± 0.08 | ||
7 | Rat | 9.3 ± 1.1 | 151 ± 35 | 0.009 | 0.54 | 0.76 ± 0.11 | |
Dog | <1 | 45.8 ± 4.8 | 0.111 | 0.62 | N.D. | ||
Monkey | 43 ± 3 | 233 ± 64 | 0.150 | 0.65 | N.D. | ||
Human | <1 | 63 ± 1 | 0.195 | 0.65 | N.D. | ||
8 | Rat | <1 | 35.2 ± 0.2 | 0.18 | 0.62 | N.D. | |
Dog | <1 | 1.6 ± 0.4 | 0.13 | 0.63 | N.D. | ||
Monkey | <1 | 14.2 ± 0.3 | 0.17 | 0.66 | N.D. | ||
Human | <1 | 1.1 ± 0.2 | 0.17 | 0.63 | N.D. | ||
9 | Rat | 1.0 ± 0.2 | 8.1 ± 1.0 | 0.268 | 0.66 | N.D. | |
Dog | 1.0 ± 0.2 | 1.0 ± 0.3 | 0.40 | 0.75 | N.D. | ||
Monkey | <1 | 24.8 ± 2.4 | 0.262 | 0.70 | N.D. | ||
Human | <1 | 1.0 ± 0.3 | 0.262 | 0.67 | N.D. | ||
10 | Rat | 15.9 ± 1.9 | 10.6 ± 1.3 | 0.007 | 0.54 | 0.55 ± 0.03 | |
Dog | 8.4 ± 3.1 | 6.9 ± 2.6 | 0.034 | 0.59 | 0.56 ± 0.01 | ||
Monkey | 26.3 ± 3.5 | 41 ± 3 | 0.163 | 0.66 | N.D. | ||
| Human | 3.9 ± 0.3 | 20 ± 1.6 | 0.088 | 0.60 | 0.51 ± 0.02 |
N.D., not determined.
↵ a Intrinsic hepatic microsomal clearance in the presence of NADPH. Results are the mean ± S.E. from two to eight separate experiments, each carried out in duplicate.
↵ b Intrinsic hepatic microsomal clearance in the presence of UDPGA. Results are the mean ± S.E. from two to eight separate experiments, each carried out in duplicate.
↵ c Unbound fraction in plasma; results are the mean of at least two determinations; S.E. values were <15%.
↵ d Blood/plasma partition ratio calculated using eq. 1.
↵ e Experimentally determined blood/plasma partition ratio; results are the mean ± S.E. from two to four separate experiments.