Research Article

Phospholipogenic Pharmaceuticals Are Associated with a Higher Incidence of Histological Findings than Nonphospholipogenic Pharmaceuticals in Preclinical Toxicology Studies

Table 1

Nominal doses and exposures from both the nonphospholipogenic compound (NP) and phospholipogenic compound (P) datasets. Averages and standard deviations (in parentheses) shown. Data from mid-doses are not shown. Average phospholipogenic plasma exposures were lower for all species across all doses than exposures from the negative dataset, but differences were not statistically significant.

Species Low dose (μmol/kg) Low Cmax (μM) Low AUC (μM·hr) High dose (μmol/kg) High Cmax (μM) High AUC (μM·hr)

Dog (NP) 89 (124) 52 (71) 297 (429) 936 (1266) 253 (334) 2561 (4457)
Dog (P) 47 (67) 9 (13) 102 (177) 467 (614) 27 (20) 335 (345)
Mouse (NP) 323 (182) 15 (16) 52 (60) 2018 (1437) 56 (71) 322 (519)
Mouse (P) 117 (83) 6 (5) 65 (80) 958 (635) 62 (108) 320 (446)
Rat (NP) 162 (356) 25 (51) 224 (671) 1351 (2659) 204 (390) 1377 (2607)
Rat (P) 235 (384) 9 (21) 117 (324) 737 (802) 26 (32) 372 (485)