Plasma and cerebrospinal fluid pharmacokinetics of pemetrexed after intravenous administration in non-human primates

Abstract

The CSF penetration of pemetrexed was less than 2% (range 0.33-1.58%), suggesting that it should be used in conjunction with other CNS preventive strategies when used in the treatment of malignancies with a predilection for CNS or leptomeningeal metastases.

Activity of pemetrexed-based regimen as first-line chemotherapy for advanced non-small cell lung cancer with asymptomatic inoperable brain metastasis: a retrospective study

“…The CSF pemetrexed concentration AUCs were consistently less than 2% of the plasma AUCs. 22 These data are highly consistent with those obtained in patients. Kumthekar et al 23 assessed pharmacokinetics and efficacy of pemetrexed in 21 patients with brain or leptomeningeal metastases.…”

Icotinib might be effective for the treatment of leptomeningeal carcinomatosis in non-small cell lung cancer with sensitive EGFR mutations

“…5,6 Systemic chemotherapeutic drugs have limitations with respect to controlling malignant cells inside the leptomeninges because they cannot easily penetrate the blood-brain barrier. 7,8 Because no effective treatments for LMC exist, the development of novel and efficient therapeutic strategies for LMC is urgently needed.…”

Activity of Pemetrexed on brain metastases from Non-Small Cell Lung Cancer

“…To date, it is not definitely known whether Pemetrexed crosses the blood-brain barrier [17]. There is only little information in the literature concerning its use in non-human primates, in which the drug exhibited a very poor penetration into the cerebrospinal fluid [18][19][20]. One of those studies also suggests that the blood-brain barrier penetration of Pemetrexed may be higher than that of Methotrexate, an antimetabolite whose mechanism of action is similar to Pemetrexed [18].…”