Pharmacokinetically-guided dosing of pemetrexed in a patient with renal impairment and a patient requiring hemodialysis

N. de Rouw*, S. Croes, R. Posthuma, D. E. Agterhuis, J. J. A. O. Schoenmaekers, H. J. Derijks, D. M. Burger, A. M. Dingemans, R. ter Heine

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

Objectives: Pemetrexed is indicated for non-small cell lung cancer and mesothelioma. Dosing is based on body surface are (BSA), while renal function is the only determinant for exposure and thus toxicity. BSA-based dosing introduces large variability in exposure and may lead to (hemato)toxicity in patients with impaired renal function. Therefore, pemetrexed is contraindicated in renal impairment. The presented cases provide proof-of concept for pharmacokinetically-guided dosing of pemetrexed in a haemodialysis patient and a patient with mild renal impairment.

Methods: The pharmacokinetic target was an area under the concentration-time curve (AUC) of 123-205 mg.h/L. Using a previously developed population pharmacokinetic model, individual pharmacokinetics were estimated.

Results: Both patients had an exposure above target after the initial dose, but a proportional dose reduction resulted in a therapeutic exposure in both patients (185 and 166 mg.h/L, respectively), that was well-tolerated. Interestingly, a threefold increase in systemic clearance of pemetrexed was observed during hemodialysis (from 1.00 L/h to 3.01 L/h), which approximates the population clearance of pemetrexed.

Conclusion: Altogether, we showed that pharmacokinetically-guided dosing of pemetrexed may be a feasible strategy for patients with lung cancer and renal impairment.

Original languageEnglish
Pages (from-to)156-158
Number of pages3
JournalLung Cancer
Volume130
DOIs
Publication statusPublished - Apr 2019

Keywords

  • Pemetrexed
  • Non-small cell lung cancer
  • Renal impairment
  • Pharmacokinetics
  • CANCER

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