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Mitiperstat is a novel myeloperoxidase inhibitor being investigated for the treatment of heart failure, metabolic dysfunction-associated steatohepatitis, and chronic obstructive pulmonary disease. Pharmacokinetic data from five clinical trials were used to develop a mitiperstat population pharmacokinetics (popPK) model. In total, 2856 plasma samples from 128 mitiperstat-treated participants were collected during the first-in-human single-ascending dose (SAD) study; multiple-ascending dose studies (MAD) in healthy volunteers, including healthy Japanese and Chinese volunteers (JCMAD); the phase 2a SATELLITE study in patients with heart failure with preserved/mildly reduced ejection fraction (HFpEF/HFmrEF); and from a study in patients with severe renal impairment. The mitiperstat concentration-time data were pooled and analyzed with the software NONMEM. The covariates considered in this analysis were baseline estimated glomerular filtration rate (eGFR), baseline body weight, baseline body mass index, sex, race (Asian or non-Asian), age, disease status (healthy volunteers or patients with HFpEF/HFmrEF), and formulation (oral suspension or tablet). The final popPK model is a two-compartment model with first-order absorption and linear elimination. Baseline body weight, disease status, Asian race, and eGFR were identified as significant covariates for apparent clearance, and age was identified as a significant covariate for apparent central volume of distribution. The final model predicts that severe renal impairment and lower body weight have the largest impact on exposure. Exposure to mitiperstat increased as eGFR declined. This popPK model constitutes an important step toward optimizing doses for efficacy and safety in the different mitiperstat development programs. Trial Registration: ClinicalTrials.gov: NCT02712372.