Exposure-Response Relationships for Toceranib in Dogs with Solid Tumors: A Pilot Study
Young-Rok Kim1,2, Ji-Hwan Park3, Kieun Bae1,4
1KU Animal Cancer Center, Konkuk University Veterinary Medical Teaching Hospital, Seoul 05029, Republic of Korea.
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 (Cmax) and trough (Cmin) concentrations were 29% and 61%, respectively. Dose-normalized Cmax did not differ among weeks 1, 4, and 12 (p = 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 Cmax, p = 0.941; average Cmax, p = 0.548). Cmax was positively but nonsignificantly associated with the risk of adverse events (week 1 Cmax, p = 0.190; average Cmax, p = 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.
Insights
Monitoring toceranib phosphate (TOC) levels in dogs with cancer can help optimize dosage and reduce side effects. This study found that TOC exposure was not clearly linked to efficacy or safety, suggesting personalized dosing is key.
Area of Science:
- Veterinary Oncology
- Pharmacokinetics
- Drug Metabolism and Disposition
Background:
- Interpatient variability in drug exposure necessitates dose adjustments for targeted therapies.
- Toceranib phosphate (TOC) is a widely used tyrosine kinase inhibitor in veterinary oncology, but its exposure-response relationships are not well understood.
- Understanding these relationships is crucial for optimizing TOC treatment in dogs with solid tumors.
Purpose of the Study:
- To evaluate the correlation between toceranib phosphate (TOC) exposure and its efficacy and safety in dogs with solid tumors.
- To determine if steady-state plasma levels of TOC are achieved within one week of administration.
- To assess the impact of pharmacokinetic monitoring on optimizing TOC dosage and minimizing adverse events.
Main Methods:
- Plasma concentrations of TOC were measured at 6 and 48 hours post-administration in dogs with solid tumors.
- Exposure-response relationships were analyzed using dose-normalized peak (Cmax) and trough (Cmin) concentrations.
- Statistical analyses were performed to correlate TOC exposure with efficacy and safety outcomes.
Main Results:
- Mean interpatient variabilities in dose-normalized Cmax and Cmin were 29% and 61%, respectively.
- Steady-state plasma levels of TOC were achieved within 1 week, as Cmax did not differ significantly between weeks 1, 4, and 12.
- Pharmacokinetic exposure at steady state was not significantly associated with efficacy or the risk of adverse events.
Conclusions:
- Toceranib phosphate (TOC) pharmacokinetic exposure at steady state was not significantly associated with efficacy or adverse events in dogs with solid tumors.
- These findings highlight the importance of pharmacokinetic monitoring for optimizing TOC dosage and reducing adverse effects.
- Clinicians should consider plasma TOC levels when managing TOC treatment in small-animal practice to personalize therapy.
