Fig. 3: Absorptive lymphatic partitioning of LP-182 involves association with lipoproteins.
From: A lymphatic-absorbed multi-targeted kinase inhibitor for myelofibrosis therapy
a Concentration of LP-182 in blood and mesenteric lymph nodes from mice 30 min following oral administration at the indicated doses. Data represent the mean ± s.e.m., n = 4 animals per dose. Statistical significance determined using multiple unpaired t-test corrected with Holm-Šidák multiple comparisons test (100 mg kg−1, p = 0.039; 200 mg kg−1, p = 0.034; 400 mg kg−1, p = 0.000094; 600 mg kg−1, p = 0.029; 800 mg kg−1, p = 0.043; 1000 mg kg−1, p = 0.036). b Concentration of LP-527, PD0316684, and LP-182 in blood and mesenteric lymph nodes from mice 4 h following oral administration at 100 mg kg−1. Data represent the mean ± s.e.m., LP-527 (n = 9), PD0316684 (n = 10), and LP-182 (n = 9) animals per group. c Enterocyte schematic showing possible routes of drug access into the blood and intestinal lymphatics in an anesthetized rat mesenteric lymph cannulation model8,37. d Kinetic profiles of LP-182 in lymphatic fluid from anesthetized rats following 1 h intra-duodenal infusion at 50 mg kg−1. Data represent the mean ± s.e.m., n = 7 animals per time point. Source data are provided as a Source Data file. e Relative percent of total LP-182 measured within chylomicron, very low-density lipoprotein (VLDL), and low-density lipoprotein/high-density lipoprotein (LDL/HDL) fractions upon separation of pooled time course lymphatic fluid by ultracentrifugation from anesthetized rats following 1 h intra-duodenal infusion of LP-182 at 50 mg kg−1. Data represent the mean ± s.e.m., n = 3 animals.
