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Hyperhydration with cisplatin does not influence pemetrexed exposure.

Nikki de Rouw1,2, Hieronymus J Derijks1,2, Luuk B Hilbrands3

  • 1Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.

British Journal of Clinical Pharmacology
|August 10, 2021
PubMed
Summary
This summary is machine-generated.

Hyperhydration during cisplatin treatment does not significantly alter pemetrexed pharmacokinetics. This study found no need for pemetrexed dose adjustments when combined with hyperhydration, ensuring consistent lung cancer treatment.

Keywords:
hyperhydrationpemetrexedpharmacokinetics

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Area of Science:

  • Pharmacology
  • Oncology
  • Clinical Pharmacy

Background:

  • Pemetrexed is a key first-line lung cancer drug, often given with cisplatin.
  • Hyperhydration is used to prevent cisplatin's kidney toxicity.
  • The impact of hyperhydration on pemetrexed pharmacokinetics is not well understood.

Purpose of the Study:

  • To evaluate hyperhydration as a factor influencing pemetrexed clearance and volume of distribution.
  • To determine if pemetrexed dose adjustments are needed during hyperhydration.

Main Methods:

  • Population pharmacokinetic analysis of 133 individuals.
  • Assessed hyperhydration's effect on pemetrexed clearance and volume of distribution.
  • Defined relevant change as >25% increase in clearance or volume.

Main Results:

  • Hyperhydration did not significantly impact pemetrexed clearance (P=0.196).
  • Hyperhydration caused a minor, non-relevant increase in pemetrexed volume of distribution (+7%, P=0.002).
  • The study had >99% power to detect a relevant change.

Conclusions:

  • Hyperhydration does not necessitate pemetrexed dose adjustments in clinical practice.
  • Pemetrexed efficacy and toxicity are unlikely to be significantly affected by hyperhydration regimens.
  • Current treatment protocols for lung cancer with pemetrexed and cisplatin can be maintained.