Pharmacokinetics and Efficacy of Multikinase Inhibitors in Solid Tumors

Multikinase inhibitors constitute a class of targeted agents designed to block multiple signalling pathways implicated in tumour growth, angiogenesis and metastasis. These small molecules are administered orally and undergo complex absorption, distribution, metabolism and excretion processes that determine systemic exposure and therapeutic index. Key pharmacokinetic parameters—such as maximum plasma concentration (Cmax), area under the concentration–time curve (AUC) and elimination half-life—are influenced by hepatic metabolism (primarily via cytochrome P450 enzymes) and membrane transporters. Inter-individual variability in drug-metabolising enzymes, transporter activity and concomitant medications can lead to unpredictable exposure, affecting both efficacy and toxicity.

Efficacy of multikinase inhibitors in solid tumours has been established across a range of indications, including hepatocellular carcinoma, renal cell carcinoma and thyroid carcinoma. Clinical benefit correlates with sustained target inhibition in tumour and stromal compartments, but is tempered by on-target adverse events—most notably hand-foot skin reaction, hypertension and gastrointestinal toxicity. Emerging strategies to optimise dosing include therapeutic drug monitoring, pharmacogenetic profiling and strategic management of drug–drug interactions to maintain exposure within a therapeutic window. Integration of pharmacokinetic and pharmacodynamic biomarkers has improved individualisation of treatment, thereby enhancing response rates and minimising severe toxicity.

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Pharmacokinetics and Efficacy of Multikinase Inhibitors in Solid Tumors publication trend

The graph below shows the total number of articles in pharmacokinetics and efficacy of multikinase inhibitors in solid tumors across all publications each year (not limited to Nature Index journals).

Technical terms

Multikinase inhibitor: A small molecule that targets multiple kinase enzymes involved in cell signalling pathways driving tumour progression.

Area under the plasma concentration–time curve (AUC): The integral of drug concentration over time, reflecting overall exposure.

Maximum plasma concentration (Cmax): The highest measured drug concentration in plasma following administration.

Elimination half-life (t1/2): The time required for plasma drug concentration to decline by half, indicating duration of action.

Drug–drug interaction: A modification of a drug’s pharmacokinetics or pharmacodynamics caused by co-administered substances.

Biomarker: A measurable indicator of drug exposure, pharmacological effect or disease state used to guide therapy.

References

1. Influence of Probenecid on the Pharmacokinetics and Pharmacodynamics of Sorafenib. Pharmaceutics (2020).
2. Cytochrome P450 3A5 polymorphism affects the metabolism of sorafenib and its toxicity for hepatocellular carcinoma cells in vitro. Human & Experimental Toxicology (2022).
3. Practicality of STAT3 Gene Polymorphisms and Sorafenib Trough Concentration as Biomarkers for Sorafenib‐Induced Hand‐Foot Skin Reaction in Hepatocellular Carcinoma. Journal of Clinical Pharmacy and Therapeutics (2023).