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Table of Contents
Vol. 5, No. 3, 2012
Issue release date: September – December
Section title: Published: November 2012
Open Access Gateway
Case Rep Oncol 2012;5:627–632
(DOI:10.1159/000345694)

Pharmacokinetic/Pharmacodynamic Analysis of a Hemodialyzed Patient Treated with 25 mg of Sunitinib

Noda S.a · Kageyama S.b · Tsuru T.b · Kubota S.b · Yoshida T.b · Okamoto K.b · Okada Y.b · Morita S.a · Terada T.a
Departments of aPharmacy and bUrology, Shiga University of Medical Science Hospital, Otsu City, Japan
email Corresponding Author

Abstract

Sunitinib has been approved for the treatment of advanced and/or metastatic renal cell carcinoma (RCC). Information on the dosage adjustment of sunitinib for patients undergoing hemodialysis is limited. Especially, efficacy and tolerance of sunitinib at a low dose in such patients are not fully understood. Thus, we examined the effect of hemodialysis on the pharmacokinetics, safety and efficacy of 25 mg of sunitinib. The patient was a 66-year-old man diagnosed with RCC and undergoing hemodialysis. He was treated with sunitinib at 25 mg daily for 4 weeks of a 6-week cycle. There were little differences in the AUC0–24 h of sunitinib and its major active metabolite SU12662 on day 17 (on hemodialysis) and day 18 (off hemodialysis) of the first cycle. The total sunitinib concentration (sunitinib and SU12662) was approximately 50 ng/ml at a steady state in every cycle. The patient’s genotype was wild type for ABCG2 421C>A, which is associated with increased sunitinib exposure. In the following two cycles of sunitinib, computed tomography scan showed a partial response of the lung metastasis. During the first cycle, the patient developed grade 2 thrombocytopenia and leukocytopenia. After four cycles of treatment, the patient developed grade 3 fatigue and the sunitinib treatment was discontinued. Our patient on hemodialysis could be safely and effectively treated with 25 mg of sunitinib, and a total sunitinib concentration of about 50 ng/ml was maintained. The pharmacokinetics of sunitinib and SU12662 were rarely affected by hemodialysis. Therapeutic drug monitoring could be helpful during sunitinib therapy, especially in a specific population.

© 2012 S. Karger AG, Basel


  

Key Words

  • Tyrosine kinase inhibitor
  • Sunitinib
  • Hemodialysis
  • Renal cell carcinoma
  • Pharmacokinetics
  • Pharmacodynamics

  

Author Contacts

Tomohiro Terada
Department of Pharmacy
Shiga University of Medical Science Hospital, Seta Tsukinowa-cho
Otsu City, Shiga 520-2192 (Japan)
E-Mail teradat@belle.shiga-med.ac.jp

  

Article Information

Published online: November 21, 2012
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 1,

  

Publication Details

Case Reports in Oncology

Vol. 5, No. 3, Year 2012 (Cover Date: September - December)

Journal Editor: Markman M. (Philadelphia, Pa.)
ISSN: 1662-6575 (Print), eISSN: 1662-6575 (Online)

For additional information: http://www.karger.com/CRO


Open Access License / Drug Dosage / Disclaimer

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Sunitinib has been approved for the treatment of advanced and/or metastatic renal cell carcinoma (RCC). Information on the dosage adjustment of sunitinib for patients undergoing hemodialysis is limited. Especially, efficacy and tolerance of sunitinib at a low dose in such patients are not fully understood. Thus, we examined the effect of hemodialysis on the pharmacokinetics, safety and efficacy of 25 mg of sunitinib. The patient was a 66-year-old man diagnosed with RCC and undergoing hemodialysis. He was treated with sunitinib at 25 mg daily for 4 weeks of a 6-week cycle. There were little differences in the AUC0–24 h of sunitinib and its major active metabolite SU12662 on day 17 (on hemodialysis) and day 18 (off hemodialysis) of the first cycle. The total sunitinib concentration (sunitinib and SU12662) was approximately 50 ng/ml at a steady state in every cycle. The patient’s genotype was wild type for ABCG2 421C>A, which is associated with increased sunitinib exposure. In the following two cycles of sunitinib, computed tomography scan showed a partial response of the lung metastasis. During the first cycle, the patient developed grade 2 thrombocytopenia and leukocytopenia. After four cycles of treatment, the patient developed grade 3 fatigue and the sunitinib treatment was discontinued. Our patient on hemodialysis could be safely and effectively treated with 25 mg of sunitinib, and a total sunitinib concentration of about 50 ng/ml was maintained. The pharmacokinetics of sunitinib and SU12662 were rarely affected by hemodialysis. Therapeutic drug monitoring could be helpful during sunitinib therapy, especially in a specific population.

© 2012 S. Karger AG, Basel


  

Author Contacts

Tomohiro Terada
Department of Pharmacy
Shiga University of Medical Science Hospital, Seta Tsukinowa-cho
Otsu City, Shiga 520-2192 (Japan)
E-Mail teradat@belle.shiga-med.ac.jp

  

Article Information

Published online: November 21, 2012
Number of Print Pages : 6
Number of Figures : 2, Number of Tables : 1,

  

Publication Details

Case Reports in Oncology

Vol. 5, No. 3, Year 2012 (Cover Date: September - December)

Journal Editor: Markman M. (Philadelphia, Pa.)
ISSN: 1662-6575 (Print), eISSN: 1662-6575 (Online)

For additional information: http://www.karger.com/CRO


Article / Publication Details

First-Page Preview
Abstract of Published: November 2012

Published online: 11/21/2012
Issue release date: September – December

Number of Print Pages: 6
Number of Figures: 2
Number of Tables: 1

ISSN: (Print)
eISSN: 1662-6575 (Online)

For additional information: http://www.karger.com/CRO


Open Access License / Drug Dosage

Open Access License: This is an Open Access article licensed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported license (CC BY-NC) (www.karger.com/OA-license), applicable to the online version of the article only. Distribution permitted for non-commercial purposes only.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.