Pharmacokinetic evaluation of pemetrexed

Expert Opin Drug Metab Toxicol. 2011 Jul;7(7):919-28. doi: 10.1517/17425255.2011.587411. Epub 2011 May 21.

Abstract

Introduction: Pemetrexed is a multi-targeted antifolate cytotoxic agent that has demonstrated activity in a number of very common cancer types including NSCLC in both first- and second-line settings and in the treatment of malignant mesothelioma.

Areas covered: This article focuses on all of the currently published pharmacokinetic data of pemetrexed reviewing a number of different scenarios and patient populations. All the articles reviewed in this manuscript are from peer-reviewed English-spoken literature without any limitations to the time of publication.

Expert opinion: Pemetrexed's clearance correlates with renal function and it may be safely used with vitamin supplementation in patients with creatinine clearance ≥ 45 ml/min. The pharmacokinetics of pemetrexed is also largely unchanged in third-space fluids and can be feasibly and safely administered in combination with several other cytotoxic or targeted agents. It is the author's opinion that pemetrexed is already a valuable cytotoxic agent which has proved useful in several malignancies. However, future trials might expand on the combined use of pemetrexed with other targeted agents that could be beneficial to other selected patients harboring relevant mutations or other biological features.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols
  • Brain / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease Models, Animal
  • Drug Evaluation
  • Drug Interactions
  • Folic Acid Antagonists / administration & dosage
  • Folic Acid Antagonists / pharmacokinetics*
  • Glutamates / administration & dosage
  • Glutamates / pharmacokinetics*
  • Guanine / administration & dosage
  • Guanine / analogs & derivatives*
  • Guanine / pharmacokinetics
  • Humans
  • Kidney Neoplasms / drug therapy
  • Liver / drug effects
  • Mesothelioma / drug therapy*
  • Pemetrexed
  • Platinum Compounds / administration & dosage
  • Platinum Compounds / pharmacokinetics
  • Tissue Distribution
  • Vitamins / administration & dosage
  • Vitamins / pharmacokinetics

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Antineoplastic Agents
  • Folic Acid Antagonists
  • Glutamates
  • Platinum Compounds
  • Vitamins
  • Pemetrexed
  • Guanine