The impact of a 1-hour time interval between pazopanib and subsequent intake of gastric acid suppressants on pazopanib exposure

Stefanie D. Krens*, Floor J. E. Lubberman, Marthe van Egmond, Frank G. A. Jansman, David M. Burger, Paul Hamberg, Walter L. Vervenne, Hans Gelderblom, Winette T. A. van Der Graaf, Ingrid M. E. Desar, Carla M. L. van Herpen, Nielka P. van Erp

*Corresponding author for this work

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Abstract

Co-treatment with gastric acid suppressants (GAS) in patients taking anticancer drugs that exhibit pH-dependant absorption may lead to decreased drug exposure and may hamper drug efficacy. In our study, we investigated whether a 1-hour time interval between subsequent intake of pazopanib and GAS could mitigate this negative effect on drug exposure. We performed an observational study in which we collected the first steady-state pazopanib trough concentration (C-min) levels from patients treated with pazopanib 800 mg once daily (OD) taken fasted or pazopanib 600 mg OD taken with food. All patients were advised to take GAS 1 hour after pazopanib. Patients were grouped based on the use of GAS and the geometric (GM) C-min levels were compared between groups for each dose regimen. Additionally, the percentage of patients with exposure below the target threshold of 20.5 mg/L and the effect of the type of PPI was explored. The GM C-min levels were lower in GAS users vs non-GAS users for both the 800 and 600 mg cohorts (23.7 mg/L [95% confidence interval [CI]: 21.1-26.7] vs 28.2 mg/L [95% CI: 25.9-30.5], P = .015 and 26.0 mg/L [95% CI: 22.4-30.3] vs 33.5 mg/L [95% CI: 30.3-37.1], P = .006). Subtherapeutic exposure was more prevalent in GAS users vs non-GAS users (33.3% vs 19.5% and 29.6% vs 14%). Sub-analysis showed lower GM pazopanib C-min in patients who received omeprazole, while minimal difference was observed in those receiving pantoprazole compared to non-users. Our research showed that a 1-hour time interval between intake of pazopanib and GAS did not mitigate the negative effect of GAS on pazopanib exposure and may hamper pazopanib efficacy.

Original languageEnglish
Pages (from-to)2799-2806
Number of pages8
JournalInternational Journal of Cancer
Volume148
Issue number11
Early online date19-Jan-2021
DOIs
Publication statusPublished - 1-Jun-2021

Keywords

  • drug-drug interaction
  • gastric acid-suppressive agents
  • omeprazole
  • pantoprazole
  • pazopanib
  • pharmacokinetics

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