Table 1

Distribution of in vitro metabolites of ABT-378 in male mouse, rat, dog, monkey, and human liver microsomal incubations

MatrixRate of Disappearance of ABT-378 (nmol·mg−1·min−1)% of Total Sample Radioactivity after a 30-min Incubation
ABT-378M-1M-2M-3M-4M-5M-6M-7M-8M-9M-10M-11M-12Other
Mouse−3.5442.092.826.837.3125.701.981.552.700.90ND0.661.472.344.31
Rat−3.8541.253.615.199.8830.801.751.701.620.950.61ND1-a 0.950.551.75
Dog−2.3959.005.690.897.5017.410.510.891.300.360.510.970.710.485.26
Monkey−9.8014.2813.051.4413.2033.522.420.691.190.332.073.267.381.2211.28
Human−2.7260.484.621.855.3918.230.760.810.67ND1-a 1.521.051.792.140.69
HHS1-b −8.041-c 55.235.441.424.9019.060.731.011.002.162.361.541.162.321.66
HLS1-d −1.061-e 74.540.25ND1-a 2.425.25ND1-a ND1-a ND1-a ND1-a ND1-a ND1-a 2.45ND1-a 15.33
  • ND, not detected; HHS, human hepatocytes; HLS, human liver slices. ABT-378 concentration was 25 μM (microsomes), 3 μM (liver slices) and 5 μM (hepatocytes).

  • 1-a Small amounts of these metabolites were detected at later time points.

  • 1-b Two-hour incubation with human hepatocytes.

  • 1-c Pmol per million hepatocytes per minute.

  • 1-d Six-hour incubation with human liver slices.

  • 1-e Pmol per liver slice per minute.