How toceranib drug levels affect dogs with solid tumors

Abstract

The existence of considerable interpatient variability in pharmacokinetic exposure necessitates dose adjustment to avoid potential adverse events and suboptimal efficacy in targeted therapy. Exposure–response relationships for toceranib phosphate (TOC), the most commonly used tyrosine kinase inhibitor in veterinary oncology, remain unclear. Correlations between TOC exposure and efficacy and safety were evaluated in dogs with solid tumors in our study. Plasma TOC was analyzed at 6 and 48 h post-administration. For the 10 dogs in the exposure–response analysis, the mean interpatient variabilities in dose-normalized peak (C_max) and trough (C_min) concentrations were 29% and 61%, respectively. Dose-normalized C_max did not differ among weeks 1, 4, and 12 (<i>p</i> = 0.414), suggesting that steady-state plasma levels can be achieved within 1 week. Pharmacokinetic exposure at steady state was not significantly associated with efficacy (week 1 C_max, <i>p</i> = 0.941; average C_max, <i>p</i> = 0.548). C_max was positively but nonsignificantly associated with the risk of adverse events (week 1 C_max, <i>p</i> = 0.190; average C_max, <i>p</i> = 0.109). These findings suggest the value of pharmacokinetic monitoring in optimizing TOC dosage and reducing its adverse effects in dogs with solid tumors. Clinicians should consider plasma TOC when managing TOC treatment in small-animal practice.