European Journal of Clinical Pharmacology

, Volume 73, Issue 2, pp 185–195 | Cite as

Effects of ranitidine (antacid), food, and formulation on the pharmacokinetics of fostamatinib: results from five phase I clinical studies

  • Talia Flanagan
  • Paul Martin
  • Michael Gillen
  • David Mathews
  • Eleanor Lisbon
  • Martin Kruusmägi
Pharmacokinetics and Disposition



Fostamatinib is an orally dosed phosphate prodrug that is cleaved by intestinal alkaline phosphatase to the active metabolite R406. Clinical studies were performed to assess the effect of food and ranitidine on exposure, to support in vitro-in vivo relationships (IVIVR) understanding and formulation transitions and to investigate absolute oral bioavailability.


A series of in vitro dissolution and clinical pharmacokinetic studies were performed to support the design and introduction of a new formulation, understand the impact of changes in in vitro dissolution on in vivo performance for two fostamatinib formulations, to characterize the effects of food and ranitidine on exposure, and determine the absolute oral bioavailability.


The in vivo performance of fostamatinib was generally insensitive to changes in in vitro dissolution performance, although marked slowing of the dissolution rate did impact exposures. Food and ranitidine had minor effects on R406 exposure that were not considered clinically relevant. The absolute oral bioavailability of fostamatinib was 54.6 %.


The absolute oral bioavailability of fostamatinib was ~55 %. Food and ranitidine had minor effects on R406 exposure. An in vitro dissolution versus clinical performance relationship was determined that supported formulation transitions.


Fostamatinib Pharmacokinetics Food effect Ranitidine DDI Absolute bioavailability SYK inhibitor 



We acknowledge Paul Severin at Covance for performing the R406 bioanalytical work.

Compliance with ethical standards

All procedures performed in studies involving human participants were approved by the independent Institutional Review Boards and in accordance with applicable regulatory requirements, Good Clinical Practice guidelines, and ethical principles that have their origins in the Declaration of Helsinki. Informed consent was obtained from all subjects prior to initiation of the studies.

Conflict of interest

Michael Gillen is an employee of AstraZeneca and hold stocks/shares in the company. Talia Flanagan is an employee of AstraZeneca. David Mathews has no conflicts of interest to declare. Eleanor Lisbon is an employee of Quintiles and holds stock/shares in the company. Martin Kruusmägi and Paul Martin are ex-employees of AstraZeneca and holds stocks/shares in the company.

Authors’ contributions

TF and PM had full access to all of the data in the studies and take responsibility for the integrity of the data and the accuracy of the data analysis. Additionally, TF, PM, and MG were involved with the study concept and design. PM and MG participated in the acquisition of data. Analysis and interpretation of data was carried out by PM and MG. All authors participated in article preparation and provided final approval of the manuscript.


These studies were sponsored by AstraZeneca.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Talia Flanagan
    • 1
  • Paul Martin
    • 2
  • Michael Gillen
    • 3
  • David Mathews
    • 4
  • Eleanor Lisbon
    • 4
  • Martin Kruusmägi
    • 5
  1. 1.AstraZeneca Pharmaceuticals, Alderley ParkCheshireUK
  2. 2.SandozHolzkirchenGermany
  3. 3.AstraZenecaGaithersburgUSA
  4. 4.Quintiles Inc.Overland ParkUSA
  5. 5.LEO PharmaBallerupDenmark

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