Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia.

In contrast to that in children, pharmacokinetic, pharmacodynamic, and safety information on pegaspargase in adults is very limited. We administered a single intravenous dose of pegaspargase (2000 IU/m2) as part of a standard frontline induction regimen to 25 adults with newly diagnosed acute lymphoblastic leukemia (ALL), and obtained serum samples on several time points. The population mean peak serum concentration of asparaginase enzymatic activity was 1 IU/mL, the elimination half-life was 7 days, and the volume of distribution was 2.

Asparagine depletion after pegylated E. coli asparaginase treatment and induction outcome in children with acute lymphoblastic leukemia in first bone marrow relapse: a Children's Oncology Group study (CCG-1941).

Purpose: Re-induction outcomes vary for children with acute lymphoblastic leukemia (ALL) and marrow relapse. We explored possible relationships among asparaginase (ASNase) activity levels, asparagine (ASN) depletion, anti-ASNase antibody titers, and response to re-induction therapy in children and adolescents with ALL and an 'early' first marrow relapse.

Patients And Methods: After appropriate informed consent, we enrolled children and adolescents 1-21 years old with ALL and first marrow relapse within 12 months of completion of primary therapy.

Lack of pharmacokinetic or pharmacodynamic interaction between memantine and donepezil.

Background: Memantine, a low- to moderate-affinity, uncompetitive N-methyl-D-aspartate receptor antagonist, was approved in the US for treatment of moderate to severe Alzheimer's disease in October 2003.

Objective: To determine whether an in vivo pharmacokinetic interaction exists between memantine and the acetylcholinesterase (AChE) inhibitor donepezil.

Methods: In this open-label, multiple-dose study, 24 healthy subjects (aged 18-35 y) received oral administration of memantine 10 mg on day 1.

A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study.

For this study, 118 children with standard-risk acute lymphoblastic leukemia (ALL) were given randomized assignments to receive native or pegylated Escherichia coli asparaginase as part of induction and 2 delayed intensification phases. Patients treated with pegaspargase had more rapid clearance of lymphoblasts from day 7 and day 14 bone marrow aspirates and more prolonged asparaginase activity than those treated with native asparaginase. In the first delayed intensification phase, 26% of native asparaginase patients had high-titer antibodies, whereas 2% of pegaspargase patients had those levels.