Cost-Neutral Optimization of Pazopanib Exposure by Splitting Intake Moments: A Prospective Pharmacokinetic Study in Cancer Patients

Clin Pharmacokinet. 2020 Jul;59(7):941-948. doi: 10.1007/s40262-020-00863-5.


Background and objective: Pazopanib is an oral tyrosine kinase inhibitor used in the treatment of renal cell carcinoma and soft-tissue sarcoma. At the approved dose of 800 mg once daily (QD), 16-20% of patients are being underdosed and at risk of decreased efficacy. This study aimed to show whether splitting intake moments, as a cost-neutral alternative to a dose increase, leads to an increased exposure.

Methods: We performed a cross-over trial comparing the pharmacokinetics of pazopanib 800 mg QD with pazopanib 400 mg twice daily. Pharmacokinetic sampling was performed at steady-state for both dosing schedules.

Results: Nine evaluable patients were included. At the 800 mg QD dosing schedule, median minimum plasma concentration (Cmin), area under the concentration-time curve from 0 to 24 h (AUC0-24h), and maximum plasma concentration (Cmax) were 23.2 mg/L (interquartile range 18.5-27.6), 773 mg h/L (557-1009), and 40.6 mg/L (36.4-56.4) compared with 41.6 mg/L (30.5-55.8, p = 0.004), 942 mg h/L (885-1419, p = 0.027), and 50.2 mg/L (46.8-72.5, p = 0.074) at 400 mg twice daily. One patient experienced a grade 3 event (i.e., diarrhea).

Conclusions: This study demonstrates that splitting intake moments of pazopanib leads to a 79% increase in Cmin, with acceptable tolerability. Therefore, this new dosing schedule offers a cost-neutral opportunity to optimize treatment in patients with low exposure.

Clinical trial registration: NL6137 ( ).

Publication types

  • Clinical Trial

MeSH terms

  • Carcinoma, Renal Cell* / drug therapy
  • Humans
  • Indazoles / administration & dosage
  • Indazoles / pharmacokinetics*
  • Kidney Neoplasms* / drug therapy
  • Prospective Studies
  • Pyrimidines / administration & dosage
  • Pyrimidines / pharmacokinetics*
  • Sulfonamides / administration & dosage
  • Sulfonamides / pharmacokinetics*


  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • pazopanib