Etoposide phosphate, the water soluble prodrug of etoposide

1996 ◽  
Vol 18 (5) ◽  
pp. 163-170 ◽  
Author(s):  
A. H. I. Witterland ◽  
C. H. W. Koks ◽  
J. H. Beijnen
Keyword(s):  
Water Soluble ◽  
Etoposide Phosphate

Phase I evaluation of a water-soluble etoposide prodrug, etoposide phosphate, given as a 5-minute infusion on days 1, 3, and 5 in patients with solid tumors.

1994 ◽  
Vol 12 (9) ◽  
pp. 1902-1909 ◽  
Author(s):  
D R Budman ◽  
L N Igwemezie ◽  
S Kaul ◽  
J Behr ◽  
S Lichtman ◽  
...  
Keyword(s):  
High Performance ◽  
Peak Plasma ◽  
Performance Status ◽  
Plasma Concentrations ◽  
Maximum Tolerated Dose ◽  
Water Soluble ◽  
High Dose ◽  
Maximum Plasma ◽  
Rapid Infusion ◽  
Etoposide Phosphate

PURPOSE To determine the toxicities, maximum-tolerated dose (MTD), and pharmacology of etoposide phosphate, a water-soluble etoposide derivative, administered as a 5-minute intravenous infusion on a schedule of days 1, 3, and 5 repeated every 21 days. PATIENTS AND METHODS Thirty-six solid tumor patients with a mean age of 63 years, performance status of 0 to 1, WBC count > or = 4,000/microL, and platelet count > or = 100,000/microL, with normal hepatic and renal function were studied. Doses evaluated in etoposide equivalents were 50, 75, 100, 125, 150, 175, and 200 mg/m2/d. Etoposide in plasma and urine and etoposide phosphate in plasma were measured by high-performance liquid chromatography (HPLC). Eleven of 36 patients were treated with concentrated etoposide phosphate at 150 mg/m2/d. RESULTS Grade I/II nausea, vomiting, alopecia, and fatigue were common. Leukopenia (mainly neutropenia) occurred at doses greater than 75 mg/m2, with the nadir occurring between days 15 and 19 posttreatment. All effects were reversible. Hypotension, bronchospasm, and allergic reactions were not observed in the first 25 patients. The MTD due to leukopenia was determined to be between 175 and 200 mg/m2/d. In 11 patients treated with concentrated etoposide phosphate, no local phlebitis was noted, but two patients did develop allergic phenomena. The conversion of etoposide phosphate to etoposide was not saturated in the dosages studied. Etoposide phosphate had peak plasma concentrations at 5 minutes, with a terminal half-life (t1/2) of 7 minutes. Etoposide reached peak concentrations at 7 to 8 minutes, with a t1/2 of 6 to 9 hours. Both etoposide phosphate and etoposide demonstrated dose-related linear increases in maximum plasma concentration (Cmax) and area under the curve (AUC). CONCLUSION Etoposide phosphate displays excellent patient tolerance in conventional dosages when administered as a 5-minute intravenous bolus. The suggested phase II dose is 150 mg/m2 on days 1, 3, and 5. The ability to administer etoposide phosphate as a concentrated, rapid infusion may prove of value both in the outpatient clinic and in high-dose regimens.

Phase I and pharmacokinetic study of a water-soluble etoposide prodrug, etoposide phosphate (BMY-40481)

1995 ◽  
Vol 31 (13-14) ◽  
pp. 2409-2411 ◽  
Author(s):  
M.J. Millward ◽  
D.R. Newell ◽  
V. Mummaneni ◽  
L.N. Igwemezie ◽  
K. Balmanno ◽  
...  
Keyword(s):  
Phase I ◽  
Pharmacokinetic Study ◽  
Water Soluble ◽  
Etoposide Phosphate

Phase I and pharmacokinetic study of etoposide phosphate by protracted venous infusion in patients with advanced cancer.

1997 ◽  
Vol 15 (2) ◽  
pp. 766-772 ◽  
Author(s):  
N Soni ◽  
N J Meropol ◽  
L Pendyala ◽  
D Noel ◽  
L P Schacter ◽  
...  
Keyword(s):  
Phase I ◽  
Advanced Cancer ◽  
Plasma Concentrations ◽  
Water Soluble ◽  
Ambulatory Setting ◽  
Infusion Pumps ◽  
Etoposide Phosphate ◽  
Clinical Resistance ◽  
Venous Infusion

PURPOSE Etoposide has schedule-dependent cytotoxic activity, and clinical resistance may be overcome with prolonged low-dose therapy. Oral bioavailability is variable, and protracted intravenous administration is limited by water insolubility, which requires large infusion volumes. Etoposide phosphate (EP) is a water-soluble prodrug that is rapidly converted in vivo to etoposide, and may be administered in concentrated solution. A phase I study was conducted to determine the toxicity, pharmacokinetics, and pharmacodynamics of EP administered as a protracted venous infusion in the ambulatory setting. METHODS Twenty-three patients with advanced cancer were treated with a continuous infusion of EP using ambulatory pumps for 6 weeks followed by a 2-week rest. Cohorts were treated with EP at 10, 20, 25, and 30 mg/m2/d. Steady-state plasma etoposide levels (Css) and stability of EP in infusion pumps were measured using high performance liquid chromatography (HPLC). RESULTS Myelosuppression, mucositis, and fatigue were dose-limiting. The maximum-tolerated dose (MTD) of EP was 20 mg/m2/d. The mean Css (+/- SD) of etoposide were 0.67 +/- 0.25, 1.14 +/- 0.24, 1.38 +/- 0.64, and 2.19 +/- 0.52 microg/mL at daily EP doses of 10, 20, 25, and 30 mg/m2, respectively. Neutropenia correlated with Css (r = 0.65, P = .008). EP was stable in infusion pumps for at least 7 days. Partial responses were observed in patients with hepatoma and non-small-cell lung cancer (one each). CONCLUSION EP may be conveniently and safely administered as a low-volume protracted venous infusion in the ambulatory setting. Cytotoxic plasma concentrations of etoposide are obtained at the MTD. The pharmacodynamic relationships observed suggest the possibility of pharmacologically based dosing of EP.

Synthesis of etoposide phosphate, BMY-40481: A water-soluble clinically active prodrug of etoposide

1994 ◽  
Vol 4 (21) ◽  
pp. 2567-2572 ◽  
Author(s):  
Mark G. Saulnier ◽  
David R. Langley ◽  
John F. Kadow ◽  
Peter D. Senter ◽  
Jay O Knipe ◽  
...  
Keyword(s):  
Water Soluble ◽  
Etoposide Phosphate

scholarly journals Theranostic etoposide phosphate/indium nanoparticles for cancer therapy and imaging

Nanoscale ◽  
2015 ◽  
Vol 7 (44) ◽  
pp. 18542-18551 ◽  
Author(s):  
Ramishetti Srinivas ◽  
Andrew Satterlee ◽  
Yuhua Wang ◽  
Yuan Zhang ◽  
Yongjun Wang ◽  
...  
Keyword(s):  
Cancer Therapy ◽  
Water Soluble ◽  
Spect Imaging ◽  
Imaging Agent ◽  
Etoposide Phosphate ◽  
Anti Cancer ◽  
Indium Nanoparticles

Etoposide phosphate, a water-soluble anti-cancer prodrug, was successfully encapsulated together with indium in nanoparticles. We have used indium both as a carrier to deliver etoposide phosphate and as a SPECT imaging agent through incorporation of111In.

A Resorcinol-Formaldehyde Resin as an Embedding Material for Electron Microscopy of Membranes

1969 ◽  
Vol 27 ◽  
pp. 328-329 ◽  
Author(s):  
J. G. Robertson ◽  
D. F. Parsons
Keyword(s):  
Electron Microscopy ◽  
Osmium Tetroxide ◽  
Neutral Lipids ◽  
Lipid Extraction ◽  
Water Soluble ◽  
Formaldehyde Resin ◽  
Electron Microscope Autoradiography ◽  
Resorcinol Formaldehyde ◽  
Major Disadvantage ◽  
Cell Organization

The extraction of lipids from tissues during fixation and embedding for electron microscopy is widely recognized as a source of possible artifact, especially at the membrane level of cell organization. Lipid extraction is also a major disadvantage in electron microscope autoradiography of radioactive lipids, as in studies of the uptake of radioactive fatty acids by intestinal slices. Retention of lipids by fixation with osmium tetroxide is generally limited to glycolipids, phospholipids and highly unsaturated neutral lipids. Saturated neutral lipids and sterols tend to be easily extracted by organic dehydrating reagents prior to embedding. Retention of the more saturated lipids in embedded tissue might be achieved by developing new cross-linking reagents, by the use of highly water soluble embedding materials or by working at very low temperatures.

Ferritin Labeled Antibody Staining of Thin Sections

1969 ◽  
Vol 27 ◽  
pp. 420-421
Author(s):  
J. D. McLean ◽  
S. J. Singer
Keyword(s):  
Biological Material ◽  
Water Soluble ◽  
Thin Sections ◽  
Antibody Staining ◽  
Thin Sectioning ◽  
Ultrathin Sections

The successful application of ferritin labeled antibodies (F-A) to ultrathin sections of biological material has been hampered by two main difficulties. Firstly the normally used procedures for the preparation of material for thin sectioning often result in a loss of antigenicity. Secondly the polymers employed for embedding may non-specifically absorb the F-A. Our earlier use of cross-linked polyampholytes as embedding media partially overcame these problems. However the water-soluble monomers used for this method still extract many lipids from the material.

The Effect of Benzene on Bluegill Olfactory Lamellae

1985 ◽  
Vol 43 ◽  
pp. 574-575
Author(s):  
D.R. Mattie ◽  
J.W. Fisher
Keyword(s):  
Surface Morphology ◽  
Soluble Fraction ◽  
Lepomis Macrochirus ◽  
Sublethal Concentration ◽  
Water Soluble ◽  
Major Constituent ◽  
Jet Fuels ◽  
Aquatic Biota ◽  
Normal Surface ◽  
Cacodylate Buffer

Jet fuels such as JP-4 can be introduced into the environment and come in contact with aquatic biota in several ways. Studies in this laboratory have demonstrated JP-4 toxicity to fish. Benzene is the major constituent of the water soluble fraction of JP-4. The normal surface morphology of bluegill olfactory lamellae was examined in conjunction with electrophysiology experiments. There was no information regarding the ultrastructural and physiological responses of the olfactory epithelium of bluegills to acute benzene exposure.The purpose of this investigation was to determine the effects of benzene on the surface morphology of the nasal rosettes of the bluegill sunfish (Lepomis macrochirus). Bluegills were exposed to a sublethal concentration of 7.7±0.2ppm (+S.E.M.) benzene for five, ten or fourteen days. Nasal rosettes were fixed in 2.5% glutaraldehyde and 2.0% paraformaldehyde in 0.1M cacodylate buffer (pH 7.4) containing 1.25mM calcium chloride. Specimens were processed for scanning electron microscopy.

An SEM study of raphide crystal initials in the leaves of vitis (grape)

1995 ◽  
Vol 53 ◽  
pp. 984-985
Author(s):  
H. J. Arnott ◽  
M. A. Webb ◽  
L. E. Lopez
Keyword(s):  
Calcium Oxalate ◽  
Water Soluble ◽  
Calcium Oxalate Crystals ◽  
Calcium Oxalate Crystal ◽  
Oxalate Crystals ◽  
Large Numbers ◽  
Sem Study ◽  
The Matrix ◽  
Crystal Cells ◽  
Crystal Idioblast

Many papers have been published on the structure of calcium oxalate crystals in plants, however, few deal with the early development of crystals. Large numbers of idioblastic calcium oxalate crystal cells are found in the leaves of Vitis mustangensis, V. labrusca and V. vulpina. A crystal idioblast, or raphide cell, will produce 150-300 needle-like calcium oxalate crystals within a central vacuole. Each raphide crystal is autonomous, having been produced in a separate membrane-defined crystal chamber; the idioblast''s crystal complement is collectively embedded in a water soluble glycoprotein matrix which fills the vacuole. The crystals are twins, each having a pointed and a bidentate end (Fig 1); when mature they are about 0.5-1.2 μn in diameter and 30-70 μm in length. Crystal bundles, i.e., crystals and their matrix, can be isolated from leaves using 100% ETOH. If the bundles are treated with H2O the matrix surrounding the crystals rapidly disperses.

Characterization of Chemical Impurities in Glutaraldehyde

1975 ◽  
Vol 33 ◽  
pp. 620-621
Author(s):  
B. J. Grenon ◽  
A. J. Tousimis
Keyword(s):  
Glutaric Acid ◽  
Spectroscopic Analysis ◽  
Aldol Condensation ◽  
Condensation Product ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Impurity Component ◽  
Chemical Impurities ◽  
Soluble Liquid

Ever since the introduction of glutaraldehyde as a fixative in electron microscopy of biological specimens, the identification of impurities and consequently their effects on biologic ultrastructure have been under investigation. Several reports postulate that the impurities of glutaraldehyde, used as a fixative, are glutaric acid, glutaraldehyde polymer, acrolein and glutaraldoxime.Analysis of commercially available biological or technical grade glutaraldehyde revealed two major impurity components, none of which has been reported. The first compound is a colorless, water-soluble liquid with a boiling point of 42°C at 16 mm. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopic analysis, this compound has been identified to be — dihydro-2-ethoxy 2H-pyran. This impurity component of the glutaraldehyde biological or technical grades has an UV absorption peak at 235nm. The second compound is a white amorphous solid which is insoluble in water and has a melting point of 80-82°C. Initial chemical analysis indicates that this compound is an aldol condensation product(s) of glutaraldehyde.

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