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Table 4 Selected population pharmacokinetic analyses of anticancer drugs with the inclusion of healthy volunteers

From: Reviewing the role of healthy volunteer studies in drug development

PMID number Treatment (MOA) Total studies included Purpose of population pharmacokinetic model Key findings Number of subjects
23834452 [74] Axitinib (VEGFR1, 2, and 3 inhibitor) 10 (all Phase 1) Estimate population parameters, evaluate effect of food, formulation, demographics, organ function, metabolic genotype Volume of distribution increased with body weight, but no impact on drug exposure warranting dose modification 337 (all healthy)
28833380 [82] Selumetinib (MEK inhibitor) 10 (all Phase 1) To determine whether the same model is suitable for all formulations and fed conditions and to understand differences in absorption and relative bioavailability with each study Confirmed previous findings on bioavailability; additional covariates discovered, none requiring dose modification 346 (all healthy, includes subjects with organ impairment)
26879594 [75] Lenvatinib (VEGFR1, 2, and 3, PDGFRβ, RET inhibitor) 15 (12-Phase 1, 2-Phase 2, 1-Phase 3) To characterize the PK profile, and identify factors to explain interindividual PK variability in healthy subjects and patients with cancer No clinically relevant covariates requiring dose adjustment (including demographics, biomarkers, co-administered agents, organ function) 779 (196 healthy, 583 patients with cancer)
26898300 [76] Sonidegib (Smo antagonist) 5 (4-Phase 1, 1-Phase 2) To develop a structural PK model in healthy subjects and in patients with cancer, characterize covariate effects, and determine sources of variability High-fat meals increased bioavailability fivefold, healthy volunteers had threefold higher clearance, no dose adjustments needed based on patient characteristics (patients with cancer) 436 (85 healthy, 351 patients with cancer)
29687244 [77] Cabozantinib (VEGFR2, RET, c-MET inhibitor) 9 (3-Phase 1, 2-Phase 2, 4-Phase 3) To analyze the combined PK data from different patient populations and HVs to assess the effect of cancer type, formulation and dose Small to moderate effect of demographic covariates on apparent clearance (CL/F); Patients with MTC had higher CL/F compared with HVs and other cancer types 1534 (140 healthy, 1394 patients with cancer)
  1. HV, healthy volunteers; MOA, mechanisms of action; MTC, medullary thyroid cancer; PDGFR, platelet-derived growth factor receptor; PK, pharmacokinetics; VEGFR, vascular endothelial growth factor receptor