Comparative pharmacokinetic/pharmacodynamic characterisation of a new pegylated recombinant E. colil-asparaginase preparation (MC0609) in Beagle dog

  title={Comparative pharmacokinetic/pharmacodynamic characterisation of a new pegylated recombinant E. colil-asparaginase preparation (MC0609) in Beagle dog},
  author={Stephan Borghorst and Georg Hempel and Sabine Poppenborg and Dieter Franke and T K{\"o}nig and Joachim Baumgart},
  journal={Cancer Chemotherapy and Pharmacology},
Key MethodPurposeA new pegylated recombinant l-asparaginase (MC0609) was designed to improve pharmacokinetic characteristics and to further reduce immunogenicity in comparison with the currently marketed pegylated Escherichia colil-asparaginase (pegaspargase, Oncaspar®).MethodsComparative pharmacokinetics (PK), bioavailability, pharmacodynamics and immunogenicity studies were performed in CD® rats and Beagle dogs after intravenous (i.v.) and intramuscular (i.m.) single-dose administration of MC0609 or…Expand
Impact of anti-PEG IgM antibodies on the pharmacokinetics of pegylated asparaginase preparations in mice.
  • Sabine Poppenborg, J. Wittmann, +4 authors F. Leenders
  • Chemistry, Medicine
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
  • 2016
Development of a Lyophilized Formulation of Pegaspargase and Comparability Versus Liquid Pegaspargase
Lyophilization improved the stability of pegaspargase without altering other physicochemical properties, permitting a prolonged shelf life of at least 2 years when stored at 2–8 °C, and may enable greater storage flexibility and allow for better management of pegspargase.
Efficacy and adverse events of continuous L-asparaginase administration for canine large cell lymphoma of presumed gastrointestinal origin.
Based on these results, continuous L-asparaginase administration appears to be a reasonable treatment option for dogs with large cell lymphoma of presumed gastrointestinal origin.
Improved pharmacokinetic characteristics and bioactive effects of anticancer enzyme delivery systems
ABSTRACT Introduction: Anticancer enzymes play important roles in cancer treatment. The anticancer enzyme has been in clinical use to treat acute lymphoblastic leukemia for many years. Other types of
Improved pharmacokinetic and pharmacodynamic profile of a novel PEGylated native Erwinia chrysanthemi L-Asparaginase
PEG-nErA showed a significantly improved half-life in vivo, which meant that L-Asparagine levels in plasma remained depleted for up to 25 days with a four-fold lower dose compared with 72 h for nErA at 400 U/kg dose.


Pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant asparaginase preparation in children with previously untreated acute lymphoblastic leukemia: a randomized phase 2 clinical trial.
It is concluded that the new recombinant asparaginase and other native Asparaginases medac are bioequivalent and have the same pharmacodynamic effects and the same direct toxicity profile in children with acute lymphoblastic leukemia.
Pharmacokinetic, pharmacodynamic and intracellular effects of PEG-asparaginase in newly diagnosed childhood acute lymphoblastic leukemia: results from a single agent window study
No changes in apoptotic parameters or in intracellular levels of twenty amino acids in leukemic cells could be measured, in contradiction to the changes found after in vitro exposure, which may be explained by the rapid removal of apoptotic cells from the circulation in vivo.
L-asparaginase pharmacokinetics and asparagine levels in cerebrospinal fluid of rhesus monkeys and humans.
Data indicate that systemic L-asparaginase therapy may be a feasible means of treating central nervous system involvement in patients with acute lymphoblastic leukemia and that there is no therapeutic advantage to using intrathecal L- asparagine.
Dose reduction of asparaginase under pharmacokinetic and pharmacodynamic control during induction therapy in children with acute lymphoblastic leukaemia
It is concluded that an Asparaginase medacTM dose reduced from the usual 10000 IU/m2 down to 5000 IU/M2 or 2500 IU/ m2, applied at 3 d intervals, was sufficient to achieve complete L‐asparagine depletion in serum.
Comparative pharmacokinetic studies of three asparaginase preparations.
The apparent t1/2 of ASNase is dependent on enzyme preparation used, but is not affected by dose or by repeated use, and patients who have had a hypersensitivity reaction to E coli ASnase have a decreased apparent t 1/2 with both E coli and PEG AsNase.
Comparison of Native E. coli and PEG Asparaginase Pharmacokinetics and Pharmacodynamics in Pediatric Acute Lymphoblastic Leukemia
The modeling suggests that by modifying dosages, comparable ASN depletion is achievable with both preparations, and it is suggested that by changing dosage levels, comparable Asparagine (ASN) depletion can be achieved by both preparations.
A population pharmacokinetic model for pegylated‐asparaginase in children
This is the first model able to predict the activity‐time course of PEG‐asparaginase at different dosing levels and can therefore be used for developing new dosing regimens.
Reduction in immunogenicity and clearance rate of Escherichia coli L-asparaginase by modification with monomethoxypolyethylene glycol.
This modified L-asparaginase may be much more useful than the native enzyme for the clinical treatments of tumors because of its reduced immunogenicity.
Drug Monitoring of PEG-Asparaginase Treatment in Childhood Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma
It is concluded that escalation of the dose of PEG-ASNase did not result in a significant prolongation of time with activity values considered therapeutic, and depending on the desired endpoint, a second administration of P EG-asparaginase seems to be more favorable than increasing the dose.