Purpose <p>First-generation PARP inhibitors, including olaparib, niraparib, and rucaparib, act as non-selective inhibitors of the PARP family, and are associated with hematological side effects. DM5167 is a selective PARP1 inhibitor, and its selectivity could reduce its side effects; however, its pharmacokinetic properties, tissue distribution, and excretion profiles remain unclear. This study aimed to characterize the pharmacokinetic properties of DM5167 to support the prediction of its pharmacokinetics in humans.</p> Method <p>The pharmacokinetics of DM5167 were assessed in mice, rats, and dogs over a dose range of 3–30&#xa0;mg/kg. Parameters included oral bioavailability, tissue distribution, plasma protein binding, enzyme inhibition, half-life in microsomes and hepatocytes across species, and <i>in vitro</i>–<i>in vivo</i> extrapolation to predict human clearance. Metabolite profiling was performed to identify whether any the human-specific metabolites.</p> Results <p>DM5167 demonstrated linear pharmacokinetics across the studied dose ranges in mice and rats. Oral bioavailability was moderate to high, and tissue distribution showed broad organ coverage. DM5167 exhibited high plasma protein binding across species, including humans, and did not inhibit cytochrome P450 enzymes. The half-life of the compound varied among species, with a notably longer half-life in humans. <i>In vitro</i>–<i>in vivo</i> extrapolation results indicated stable predicted clearance values in humans, and metabolite profiling did not reveal any human-specific metabolites.</p> Conclusion <p>DM5167 exhibited a favorable pharmacokinetic profile <i>in vivo</i> and <i>in vitro</i>. These findings support its potential for further clinical development and provide valuable insights to guide future preclinical and clinical studies of DM5167 and other PARP inhibitors.</p>