Intrapleural Administration of Pemetrexed: A Pharmacokinetic Study in an Animal Model

Abstract

While intravenous and intrapleural administration of pemetrexed yielded similar AUC and CL, the intrapleural route yielded a significantly lower C(max). As Cmax is a determinant of pemetrexed toxicity, intrapleural administration might offer a means of widening the effective therapeutic index of the drug by improving tolerability. Future studies are needed to confirm this hypothesis in malignant pleural mesothelioma patients.

Intrapleural administration of lipoplatin in an animal model

“…This route of administration might consequently increase the treatment efficacy while decreasing toxicity [17]. Several drugs have been used intrapleurally such as platinum compounds [18,19], etoposide [20], paclitaxel [21] and pemetrexed [22]. We hypothesized that, compared with the intravenous route, intrapleural administration of lipoplatin would both increase pleural tissue exposure and decrease systemic exposure to the drug.…”

Intrapleural polymeric films containing cisplatin for malignant pleural mesothelioma in a rat tumour model: a preliminary study☆

“…Thereafter, we are interested in assessing the potential effect of pemetrexed loaded onto our polymeric films (alone and in association with cisplatin) in this rat mesothelioma model (protocol approved by the local veterinary committee). Recently, Greiller et al performed a study on rats with the aim of evaluating the pharmacokinetics of pemetrexed administered intrapleurally compared with intravenous administration [25]. They concluded that intrapleural and intravenous routes provided similar area under the plasma concentration-time curve (AUC) and total body clearance but a significantly lower maximum plasma concentration, and therefore might improve patient tolerance to pemetrexed.…”

Assessment of cisplatin concentration and depth of penetration in human lung tissue after hyperthermic exposure†

“…In future studies, combinations of chemotherapeutic drugs, such as cisplatin with gemcitabine or cisplatin with pemetrexed, will be analysed, as combination chemotherapy appears to have a greater benefit than single-agent therapy [8,23,25]. Finally, clinical data evidence and prospective trials to confirm these basic science results are still lacking.…”