Investigation of the release behavior of DEHP from infusion sets by paclitaxel-loaded polymeric micelles

Kim, Sung Chul; Yoon, Hye Jeong; Lee, Jang-Won; Yu, Jae-Won; Park, Eun-Seok; Chi, Sang-Cheol

doi:10.1016/j.ijpharm.2005.01.011

Cited by 36 publications

(25 citation statements)

References 42 publications

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“…In preclinical studies, Genexol-PM showed a threefold higher MTD value, which resulted in significantly higher tumor drug concentrations and reductions in tumor volume than CrEL-based paclitaxel in xenografted animal studies [11]. Genexol-PM also resulted in significantly lower leaching of a plasticizer from infusion sets compared to CrEL-based paclitaxel [16]. In addition to these preclinical reports, a phase I study of Genexol-PM established 390 mg/m 2 as the MTD and 300 mg/m 2 as the recommended dose [10], approximately two times higher than the MTD of CrEL-based paclitaxel.…”

Section: Discussionmentioning

confidence: 99%

Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer

Lee

Chung

et al. 2007

Breast Cancer Res Treat

475

267

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Genexol-PM is a novel Cremophor EL-free polymeric micelle formulation of paclitaxel. This single arm, multicenter phase II study was designed to evaluate the efficacy and safety of Genexol-PM in patients with histologically confirmed metastatic breast cancer (MBC). Forty-one women received Genexol-PM by intravenous infusion at 300 mg/m2 over 3 h every 3 weeks without premedication until disease progression or intolerability. A total of 331 chemotherapy cycles were administered, with a median of 8 cycles per patient (range, 1-16). Overall response rate was 58.5% (95% CI: 43.5-72.3) with 5 complete responses and 19 partial responses. Thirty-seven patients who received Genexol-PM as a first-line therapy for their metastatic disease showed a response rate of 59.5% (95% CI: 43.5-73.7), and two responses were reported in four patients treated in the second-line setting for their metastatic disease. The median time to progression (TTP) for all patients was 9.0 months (range, 1.0-17.0+ months). Grade 3 non-hematologic toxicities included sensory peripheral neuropathy (51.2%), and myalgia (2.4%). Eight patients (19.5%) experienced hypersensitivity reactions, with grade 3 in two patients. Hematologic toxicities were grade 3 and 4 neutropenia (51.2 and 17.1%, respectively), and grade 1 and 2 thrombocytopenia (22.0%). Notably, no febrile neutropenia was observed. Genexol-PM appears a promising new paclitaxel in view of significant efficacies. Further trials with different dosing schedules, durations of delivery, or in combination with other drugs are warranted.

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Section: Discussionmentioning

confidence: 99%

Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer

Lee

Chung

et al. 2007

Breast Cancer Res Treat

475

267

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“…Taxol®, Paxene®) include a mixture of Cremophor EL (polyoxyethylated castor oil) and ethanol (1:1, w/w) as solvent [10]. However, the use of Cremophor EL is associated with hypersensitivity reactions [11] and causes leakage of plasticizers from polyvinyl chloride (PVC) infusion bags and polyethylene tubing [12]. In addition, it has been demonstrated that this pharmaceutical excipient alters the pharmacokinetic behaviour of many drugs administered intravenously, including paclitaxel, by increasing the systemic exposure to the drug and reducing the systemic clearance [13].…”

Section: Introductionmentioning

confidence: 99%

Oral administration of paclitaxel with pegylated poly(anhydride) nanoparticles: Permeability and pharmacokinetic study

Zabaleta

Ponchel

Salman

et al. 2012

European Journal of Pharmaceutics and Biopharmaceutics

107

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The aim of this work was to study the potential of pegylated poly(anhydride) nanoparticles as carriers for the oral delivery of paclitaxel (PTX). Paclitaxel is an anticancer drug, ascribed to the class IV of the Biopharmaceutical Classification system, characterised for its low aqueous solubility and to act as a substrate of the P-glycoprotein and cytochrome P450. For the pegylation of nanoparticles, three different poly(ethylene glycol) (PEG) were used: PEG 2000 (PTX-NP2), PEG 6000 (PTX-NP6) and PEG 10000 (PTX-NP10). The transport and permeability of paclitaxel through the jejunum mucosa of rats was determined in Ussing chambers whereas its oral bioavailability was studied in rats. The loading of PTX in pegylated nanoparticles increased between 3 and 7-times the intestinal permeability of paclitaxel through the jejunum compared with the commercial formulation Taxol®. Interestingly, the permeability of PTX was significantly higher for PTX-NP2 and PTX-NP6 than for PTX-NP10. In the in vivo studies similar results were obtained. When PTX-NP2 and PTX-NP6 were administered to rats by the oral route, sustained and therapeutic plasma levels of paclitaxel for at least 48-h were observed. The relative oral bioavailability of paclitaxel delivered in nanoparticles was calculated to be 70% for PTX-NP2, 40% for PTX-NP6 and 16% in case of PTX-NP10. All of these observations would be related with both the bioadhesive properties of these carriers and the inhibitory effect of PEG on the activity of both P-gp and P450 cytochrome.

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“…Leaching kinetics of DEHP and other toxic compounds to the infused solution/emulsion is dependent on the design of the infusion set and on the composition of its individual parts (the length and the thickness of the tube, the size of the flashball part), infusion volume and speed, etc. (Haishima et al, 2005;Hanawa et al, 2003;Kim et al, 2005). As a result, concentrations of DEHP in the central circulation will be the highest in patients with low body weight (pediatric patients; due to the small volume of DEHP distribution) that are frequently receiving lipophilic preparations (e.g., TPN) using infusion sets with high content of plasticizers.…”

Section: Relevance Of the Findings Of This Study To The In Vivo Toxicmentioning

confidence: 99%

Mechanisms of cell death induced by infusion sets leachables in in vitro experimental settings

Kozlovskaya

Stepensky

2015

International Journal of Pharmaceutics

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Investigation of the release behavior of DEHP from infusion sets by paclitaxel-loaded polymeric micelles

Cited by 36 publications

References 42 publications

Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer

Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer

Oral administration of paclitaxel with pegylated poly(anhydride) nanoparticles: Permeability and pharmacokinetic study

Mechanisms of cell death induced by infusion sets leachables in in vitro experimental settings

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