A5030283472- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Antibiotics Pharmacokinetics and Efficacy
- Multiple Myeloma Research and Treatments
- Drug Transport and Resistance Mechanisms
- Cancer therapeutics and mechanisms
- Renal Transplantation Outcomes and Treatments
- Pharmaceutical studies and practices
- Cancer Treatment and Pharmacology
- Antifungal resistance and susceptibility
- Childhood Cancer Survivors' Quality of Life
- Chronic Myeloid Leukemia Treatments
- Analytical Methods in Pharmaceuticals
- Pharmacogenetics and Drug Metabolism
- Adolescent and Pediatric Healthcare
- Acute Myeloid Leukemia Research
- Drug-Induced Hepatotoxicity and Protection
- Heparin-Induced Thrombocytopenia and Thrombosis
- Chemotherapy-induced organ toxicity mitigation
- Chronic Lymphocytic Leukemia Research
- Blood disorders and treatments
- Cytomegalovirus and herpesvirus research
- Adenosine and Purinergic Signaling
- Herpesvirus Infections and Treatments
- Pneumocystis jirovecii pneumonia detection and treatment
Children's Hospital at Westmead
2015-2024
The University of Sydney
2001-2024
Sydney Children's Hospital
2022
Boston Children's Hospital
1999
Women's Hospital
1997
A population pharmacokinetic model of liposomal amphotericin B (L-AmB) in pediatric patients with malignant diseases was developed and evaluated. Blood samples were collected from 39 oncology who received multiple doses L-AmB a dose range 0.8 to 5.9 mg/kg body weight/day. The patient cohort had an average age 7 years (range, 0.2 17 years) weighed 28.8 +/- 19.8 kg. Population analyses performed NONMEM software. Pharmacokinetic parameters, interindividual variability (IIV), between-occasion...
To i) investigate the pharmacokinetics of total and unbound plasma melphalan using a population approach, ii) identify clinical factors that affect disposition iii) evaluate role exposure in melphalan-related toxicity disease response.
High dose melphalan (HDM) and autologous stem cell transplantation (ASCT) retains a central role in the treatment of myeloma. The aim this study was to determine whether HDM exposure (area under concentration vs. time curve, AUC), is significantly associated with transplant outcomes.
Intravenous busulfan is widely used as part of myeloablative conditioning regimens in children and young adults undergoing allogeneic hematopoietic cell transplantation (HCT). Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) a serious clinical problem observed with busulfan-based HCT. The development VOD/SOS may be associated exposure. Getting more insight into the association between exposure enables further optimization dosing treatment strategies. objective this...
Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluated prevalence antibodies PEG among patients with acute lymphoblastic leukemia (ALL) prior to and/or immediately after their first dose E.coli asparaginase (PEG-ASNase). Serum samples 701 children, 673 primary ALL, 28 relapsed and 188 adults ALL were analyzed for anti-PEG IgG IgM. Measurements 58 infants served as reference define cut-points antibody-positive...
To examine inter- and intrapatient variability in the pharmacokinetics of intravenous (i.v.) busulphan given as a single daily dose to children with malignant (n = 19) nonmalignant 21) disease.Busulphan (120 mg m(-2), 130 m(-2) or 3.2 kg(-1)) was administered over median 2.1 h. Blood samples (4-10) were collected after first dose, concentrations measured pharmacokinetic parameters, including clearance (CL) area under concentration-time curve (AUC), determined using Kinetica software...
ABSTRACT In a prospective, randomized clinical trial, the toxicity of 1 mg amphotericin B (AmB) per kg body weight day infused in 5% dextrose was compared with that AmB lipid emulsion children malignant disease. an analysis 82 who received full course 6 days or more (117 courses), it shown there were significant increases plasma urea and creatinine concentrations potassium requirement after therapy both emulsion, being no difference between two methods administration. An intent-to-treat...
Background: In the international AIEOP-BFM ALL 2009 trial, asparaginase (ASE) activity was monitored after each dose of pegylated Escherichia coli ASE (PEG-ASE). Two methods were used: aspartic acid β-hydroxamate (AHA) test and medac (MAAT). As latter method overestimates PEG-ASE because it calibrates using E. ASE, comparison performed samples from trial. Methods: activities determined MAAT AHA in 2 sets (first set: 630 second 91 samples). Bland–Altman analysis on ratios between tests. The...
Abstract Busulfan (Bu) is a common component of conditioning regimens before hematopoietic stem cell transplantation (HSCT) and known for high interpatient pharmacokinetic (PK) variability. This study aimed to develop externally validate multicentric, population PK (PopPK) model intravenous Bu in pediatric patients HSCT first the influence glutathione‐s‐transferase A1 ( GSTA1 ) polymorphisms on Bu's large multicentric while accounting fludarabine (Flu) coadministration and, second, establish...
Vincristine (VCR) is widely used to treat patients with malignant disease; among the treated VCR are children brain tumors. In vitro studies have demonstrated that cytotoxic activity of related both extracellular concentration and duration exposure. The attainment higher plasma concentrations by injecting larger bolus doses has been limited concerns about neurotoxicity. One possible alternative strategy for enhancing antitumor efficacy involves prolonging in vivo Therefore, authors explored...
What is already known about this subject • In one of the largest studies in children to date, we have published a paper that has described pharmacokinetics melphalan using two‐stage approach. study adds The current follow‐up which population pharmacokinetic model for developed and validated children. There been no other analyses on given as short infusion. Additionally, nomogram produced guide dosing. Aim To develop with malignant diseases evaluate limited sampling strategies melphalan....
To characterize the population pharmacokinetics of mycophenolic acid (MPA) and evaluate dose regimens using a simulation approach accepted therapeutic drug monitoring targets in children young people undergoing blood or marrow, kidney liver transplantation.MPA concentration-time data were collected an age specific sampling protocol over 12h. Some patients provided randomly timed but accurately recorded samples. Total unbound MPA measured by HPLC. NONMEM was employed to analyze...
Aims To construct a population pharmacokinetic model for the antifungal agent, amphotericin B (AmB), in children with malignant diseases. Methods A two compartment AmB was developed using concentration‐time data from 57 aged between 9 months and 16 years who had received 1 mg kg −1 day doses either dextrose (doseform=1) or lipid emulsion (doseform=2). P‐Pharm (version 1.5) used to estimate basic parameters, identify covariates significant relationships parameters Covariate model. The...
A novel assay for the determination of l-asparaginase activity in human plasma is described that based on HPLC quantitation l-aspartic acid produced during enzyme incubation. Methods monitoring l-asparagine depletion are also described. Chromatography acid, and l-homoserine (the internal standard) involved derivatization with o-pthaldialdehyde, then separation from other amino acids a Phenomenex Luna C(18) column using 1 mL/min flow rate mobile phase consisting di-potassium hydrogen...
Abstract A simple, accurate and sensitive HPLC method was developed for measuring total unbound mycophenolic acid (MPA) in human plasma. Total MPA extracted by protein precipitation ultrafiltration used to assess concentrations. The supernatant (20 µL) or ultrafiltrate (100 injected onto a C 18 column with mobile phase of 0.05 m sodium phosphate buffer (pH 2.31)–acetonitrile (55:45, v/v MPA; 50:50 MPA) UV detection at 254 nm. extraction recovery over 93% reproducible. assay linear the...
Aim To analyse the pharmacokinetics of melphalan in 52 children (0.3–18 years) and determine whether any clinical factors affect pharmacokinetic parameters Additionally, to examine a test dose can predict full dose, when there are 5 intervening days carboplatin therapy. Methods Melphalan concentrations were measured 14 blood samples collected from each child following doses ranging 30 180 mg m −2 . The analysed with Kinetica 4.0. Results Children who did not have ( n = 27) had median...
ABSTRACT Acyclovir is effective in the prevention and treatment of herpes simplex virus (HSV) varicella-zoster (VZV) infections. The aim this study was to characterize population pharmacokinetics acyclovir observed following with intravenous oral valacyclovir (valaciclovir) young people malignancy. Plasma concentration-time data were collected from 43 patients (age range, 9 months 20 years) who had been given multiple doses (5 mg/kg body weight) and/or (10 mg/kg). Nonlinear mixed-effect...
Treosulfan (l-threitol-1,4-di-methanesulfonate) is a prodrug of bifunctional alkylating agent that being used increasingly in pediatric bone marrow transplantation regimens. The activation pathway complex reaction, which consists two consecutive reactions leading to epoxybutane derivatives are responsible for DNA alkylation. A simple, sensitive high performance liquid chromatography method the determination sum treosulfan and its epoxy metabolites by UV detection after derivatization with...