A5036582350- Glioma Diagnosis and Treatment
- Brain Metastases and Treatment
- Pharmacological Effects and Toxicity Studies
- Acute Lymphoblastic Leukemia research
- Cancer therapeutics and mechanisms
- Antibiotics Pharmacokinetics and Efficacy
- Epilepsy research and treatment
- Drug Transport and Resistance Mechanisms
- Cerebrospinal fluid and hydrocephalus
- Nanoplatforms for cancer theranostics
- DNA Repair Mechanisms
- Nanoparticle-Based Drug Delivery
- Cancer Treatment and Pharmacology
- Lung Cancer Research Studies
- Bipolar Disorder and Treatment
- Chronic Lymphocytic Leukemia Research
- Multiple Sclerosis Research Studies
- Neuroblastoma Research and Treatments
- Pharmacogenetics and Drug Metabolism
- Head and Neck Surgical Oncology
- Neuroendocrine Tumor Research Advances
- Lung Cancer Treatments and Mutations
- Histone Deacetylase Inhibitors Research
- HIV/AIDS drug development and treatment
- Radiopharmaceutical Chemistry and Applications
National Institutes of Health
1988-2023
National Cancer Institute
2006-2022
Center for Cancer Research
2017-2020
St. Jude Children's Research Hospital
2005
Children's Hospital & Medical Center
2005
Children's Cancer Center
2005
Journal Article Fluconazole Penetration into Cerebrospinal Fluid: Implications for Treating Fungal Infections of the Central Nervous System Get access Carola A. S. Arndt, Arndt Section Leukemia Biology and Infectious Diseases, Pediatric Branch, National Cancer Institute, Institutes Health, Bethesda, Maryland Search other works by this author on: Oxford Academic PubMed Google Scholar Thomas J. Walsh, Walsh Please address requests reprints to Dr. Building 10, Room 13N240, 20892. Cynthia Lester...
The pharmacokinetics of subcutaneously administered methotrexate was studied as a parenteral alternative to oral administration. An initial feasibility study performed in Rhesus monkeys comparing the subcutaneous route intravenous (IV) injection and dose completely absorbed sustained-release effect observed when compared with IV dose. No local or systemic toxicities resulted from animals. Twelve children acute lymphoblastic leukemia on maintenance therapy protocols prescribing either 7.5...
Abstract Purpose: Describe and compare the central nervous system pharmacology of platinum analogues, cisplatin, carboplatin, oxaliplatin develop a pharmacokinetic model to distinguish disposition active drug from inert species. Experimental Design: Oxaliplatin (7 or 5 mg/kg), cisplatin (2 carboplatin (10 mg/kg) was given i.v. Serial plasma cerebrospinal fluid (CSF) samples were collected over 24 hours. Plasma ultrafiltrates prepared immediately. Platinum concentrations measured using atomic...
The novel methotrexate (MTX) rescue agent carboxypeptidase-G(2) (CPDG(2)) converts >98% of plasma MTX to 2, 4-diamino-N(10)-methylpteroic acid (DAMPA) and glutamate in patients with MTX-induced renal failure delayed excretion. DAMPA is eliminated more rapidly than these patients, suggesting nonrenal elimination. pharmacokinetics metabolism were studied four nonhuman primates reverse-phase HPLC UV, photodiode array detection, mass spectroscopy. mean peak concentration was 51 microM the...
Abstract Purpose: Imatinib mesylate (Gleevec, Glivec, STI571, imatinib) is a potent tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors. The role imatinib in malignant gliomas other solid tumors being evaluated. We used nonhuman primate model that highly predictive cerebrospinal fluid penetration drugs humans to study pharmacokinetics plasma (CSF) after i.v. p.o. administration. Experimental Design: Imatinib, 15 mg/kg over...
Preclinical studies of mafosfamide, a preactivated cyclophosphamide analog, were performed to define tolerable and potentially active target concentration for intrathecal (IT) administration. A phase I pharmacokinetic study IT mafosfamide was determine dose subsequent II trials.In vitro cytotoxicity in MCF-7, Molt-4, rhabdomyosarcoma cell lines. Feasibility nonhuman primates. These preclinical followed by trial patients with neoplastic meningitis. There five levels ranging from 1 mg 6.5 mg....
The carboxypeptidase G class of enzymes rapidly hydrolyze methotrexate (MTX) into the inactive metabolites 4-deoxy-4-amino-N10-methylpteroic acid (DAMPA) and glutamate. This study evaluated use carboxypeptidase-G2 (CPDG2) as a potential intrathecal (IT) rescue agent for massive IT MTX overdose. CSF pharmacokinetics with without CPDG2 was studied in adult rhesus monkeys (Macaca mulatta) using nontoxic 5 mg dose (equivalent to 50 humans). Without rescue, peak concentration 2,904 +/- 340...
PURPOSE Intralumbar methotrexate is one of the primary therapeutic modalities for prevention and treatment meningeal leukemia. However, distribution to ventricles limited highly variable following intralumbar dosing, cytotoxic concentrations are not always achieved or sustained in ventricular CSF. We used a nonhuman primate model determine effect body position on caudal an dose methotrexate. METHODS Methotrexate (1.0 mg) was administered by injection four animals, which were then immediately...
Abstract The provisioning of foraging opportunities to primates has been shown be an effective means enriching the laboratory environment. In this study artificial turf was used as substrate for a particulate food given subjects environmental enrichment technique. Eight rhesus monkeys exhibited significant reduction in behavioural pathology when allowed extend amount time they spent consummatory activities. An increasing trend with concomitant decline aberrant behaviour over period six...
PURPOSE Carboxypeptidase-G2 (CPDG2) is a bacterial enzyme that rapidly hydrolyzes methotrexate (MTX) into inactive metabolites. As an alternative form of rescue after high-dose MTX (HDMTX), CPDG2 has more potential advantages than standard leucovorin (LV) rescue. In this study, the plasma pharmacokinetics with and without were evaluated in adult rhesus monkeys. MATERIALS AND METHODS The determined groups animals had received 300-mg/m2 loading dose followed by 60-mg/m2/h infusion during...
We measured zidovudine concentrations in blood, muscle, and brain extracellular fluid (ECF) by microdialysis serum ultrafiltrate cerebrospinal (CSF) samples during a continuous intravenous infusion (15 mg/kg/h) after bolus dosing (50–80 mg/kg over 15 min) nonhuman primates to determine whether CSF drug penetration is valid surrogate for blood-brain barrier penetration. Recovery was estimated vivo zero net flux the retrodialysis dosing. In recovery tissue-dependent lower than blood or muscle....
The bioavailability of oral 6-mercaptopurine (6MP) at standard doses is very low, largely as a result extensive first-pass metabolism by xanthine oxidase. Fewer than one third patients achieve 6MP plasma concentrations known to be cytocidal in vitro (>1 μmol/L). Studies have suggested that can saturated higher 6MP. To determine whether saturation occurs vivo clinically used and enhanced increasing the dose, different was studied first rhesus monkeys then children with acute lymphoblastic...
The pharmacokinetics of subcutaneous bolus and continuous infusion azidothymidine (AZT) was studied in rhesus monkeys. Three animals received 100 mg/m2 as a injection both intravenously subcutaneously, with the order administration randomly determined. Two 25 per h for 12 or 24 h. AZT measured plasma by reverse-phase high-pressure liquid chromatographic assay. Following intravenous administration, elimination rapid, mean half-life 1.2 clearance 318 ml/min m2 (range, 200 to 441 m2). dose...