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Plasma filtration for the controlled removal of liposomal therapeutics - From the apheretic site of view
M. Blaha, J. Martinkova, M. Lanska, S. Filip, J. Malakova, O. Kubecek, J. Bezouska, J. Spacek,
Language English Country Netherlands
Document type Journal Article
Grant support
NV16-30366A
MZ0
CEP Register
- MeSH
- Drug Resistance, Neoplasm MeSH
- Adult MeSH
- Doxorubicin administration & dosage adverse effects analogs & derivatives blood pharmacology MeSH
- Infusions, Intravenous MeSH
- Middle Aged MeSH
- Humans MeSH
- Ovarian Neoplasms blood diagnosis drug therapy MeSH
- Polyethylene Glycols administration & dosage adverse effects pharmacology MeSH
- Drug Compounding MeSH
- Antibiotics, Antineoplastic administration & dosage adverse effects blood pharmacokinetics MeSH
- Aged MeSH
- Tissue Distribution MeSH
- Plasma Exchange methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: Nanoparticle-based drug delivery systems can overcome the dose-limited toxicity of cytostatics. Pegylated doxorubicin-containing liposomes (PLD) are able to reduce cardiotoxicity. PLD quickly (in 2 days) attains therapeutic concentration in tumorous tissue (kinetic targeting), while its distribution in normal tissue, which is a cause of mucocutaneous toxicity (MCT), is delayed. We examined PLD extracorporeal removal effectivity, using plasma filtration (PF) to determine whether the drug could be withheld prior to its organ distribution responsible for MCT toxicity. METHODS: Nine patients suffering from platinum-resistant ovarian cancer were treated with a infusion of 50 mg/m2of PLD/cycle - for four cycles q4w. Over 44 (46)-47 (49) hours postinfusion, the patients (14 cycles in total) underwent PF using the cascade method. Doxorubicin blood concentration was monitored by the HPLC method during 116 h. Individual pharmacokinetic parameters of doxorubicin were estimated. RESULTS: Over 44 (46)-47 (49) hours postinfusion, a single one-volume plasma filtration removed 35 (22-45) % of the remaining doxorubicin amount in the body. Symptoms of MCT - PPE-like syndrome (grade 3) appeared in one patient. Only one adverse reaction (1/14-7%) - short-term malaise and nausea - was reported as being related to PF. CONCLUSION: PF does remove a clinically important amount of doxorubicin in a kinetic targeting approach, which can be a useful tool for the increased efficacy and tolerability of therapy with PLD. There were no serious signs of drug toxicity and/or PF-related adverse events.
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- $a Blaha, M $u 4th Department of Internal Medicine - Hematology, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic. Electronic address: blaham@email.cz.
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- $a INTRODUCTION: Nanoparticle-based drug delivery systems can overcome the dose-limited toxicity of cytostatics. Pegylated doxorubicin-containing liposomes (PLD) are able to reduce cardiotoxicity. PLD quickly (in 2 days) attains therapeutic concentration in tumorous tissue (kinetic targeting), while its distribution in normal tissue, which is a cause of mucocutaneous toxicity (MCT), is delayed. We examined PLD extracorporeal removal effectivity, using plasma filtration (PF) to determine whether the drug could be withheld prior to its organ distribution responsible for MCT toxicity. METHODS: Nine patients suffering from platinum-resistant ovarian cancer were treated with a infusion of 50 mg/m2of PLD/cycle - for four cycles q4w. Over 44 (46)-47 (49) hours postinfusion, the patients (14 cycles in total) underwent PF using the cascade method. Doxorubicin blood concentration was monitored by the HPLC method during 116 h. Individual pharmacokinetic parameters of doxorubicin were estimated. RESULTS: Over 44 (46)-47 (49) hours postinfusion, a single one-volume plasma filtration removed 35 (22-45) % of the remaining doxorubicin amount in the body. Symptoms of MCT - PPE-like syndrome (grade 3) appeared in one patient. Only one adverse reaction (1/14-7%) - short-term malaise and nausea - was reported as being related to PF. CONCLUSION: PF does remove a clinically important amount of doxorubicin in a kinetic targeting approach, which can be a useful tool for the increased efficacy and tolerability of therapy with PLD. There were no serious signs of drug toxicity and/or PF-related adverse events.
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- $a Martinkova, J $u Department of Oncology and Radiotherapy, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic.
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- $a Lanska, M $u 4th Department of Internal Medicine - Hematology, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic.
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- $a Filip, S $u Department of Oncology and Radiotherapy, Charles University in Prague, Medical Faculty and University Hospital in Hradec Králové, Czech Republic.
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- $a Malakova, J $u Department of Clinical Biochemistry and Diagnostics of University Hospital in Hradec Králové, Czech Republic.
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