Clinical pharmacokinetics of afatinib: A systematic review

Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure.

Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria.

Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC_0-24 and C_max values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The C_max of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The C_max decreases 31.45% when given with pemetrexed. Both the AUC_0-24 and C_max increase in NSCLC and tumor state. The AUC_0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC_0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients.

This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.