Lost in third space: altered tyrosine-kinase inhibitor pharmacokinetics in a patient with malignant ascites.

Autor: Krens SD; Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands. s.d.krens@amsterdamumc.nl., Mulder SF; Department of Medical Oncology, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands., van Erp NP; Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 2022 Feb; Vol. 89 (2), pp. 271-274. Date of Electronic Publication: 2021 Dec 01.
DOI: 10.1007/s00280-021-04377-0
Abstrakt: Background: Pazopanib and sunitinib are oral tyrosine kinase inhibitors (TKI) approved for the treatment of renal cell carcinoma. For both oncolytics, a clear target trough concentration level in plasma has been defined above which improved clinical efficacy can be expected. However, many factors can alter TKI exposure, including disease characteristics.
Case: A 79-year old male with metastatic papillary renal cell carcinoma and malignant ascites was treated with pazopanib. Initially, treatment with pazopanib at adequate trough concentrations resulted in regression of ascites. After a 6-month puncture-free interval, paracenteses were again required and the plasma trough concentration of pazopanib had decreased to 5 mg/L without any dose adjustments. Despite a dose increase, pazopanib levels remained subtherapeutic and could not prevent new paracenteses. Pazopanib concentrations in the drained ascites fluid were comparable to plasma concentrations and remained high also after treatment discontinuation. This observation suggests that the ascites compartment may act as a third space in which pazopanib accumulates. During subsequent treatment with sunitinib, a similar distribution over ascites fluid was observed.
Conclusion: Presence of ascites or pleural effusion in patients treated with TKIs may lead to subtherapeutic plasma exposure, which may hamper treatment efficacy. Measuring TKIs plasma concentrations regularly during treatment is essential to identify patients with subtherapeutic exposure.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
Externí odkaz: