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1.
J E Paciga S A Shelley J E Paterson R A Knuppel J C Scerbo J U Balis 《Annals of clinical and laboratory science》1988,18(2):141-147
Dot immunobinding assays for the quantitation of two classes of proteins associated with lung surfactant phospholipids in human amniotic fluid are described. With the use of these assays it was determined that the two classes of surfactant proteins accumulate in the amniotic fluid at the same rate. The concentrations of disaturated phosphatidylcholine and the surfactant-associated proteins are less closely correlated. Centrifugation of amniotic fluids either before or after freezing resulted in a loss ranging from 10 to 35 percent of both surfactant disaturated phosphatidylcholine and proteins depending on the relative centrifugal force used. Preterm amniotic fluids contained significantly less of both surfactant-associated proteins, as well as disaturated phosphatidylcholine, than did term amniotic fluids which suggests that the use of these specific protein markers may enhance the assessment of fetal lung maturity. 相似文献
2.
Fetuses were obtained on the 28th gestational day from pregnant New Zealand white rabbits treated daily, on the 24th through the 27th gestational day, with pilocarpine HCl, 5 mg/kg in saline, or saline alone. Lung fragments from these fetuses were incubated for two hours in medium containing 3H-thymidine. Scintillation autoradiography of 1-μm-thick sections of these fetal lungs revealed that the lung tissue from pilocarpine-treated fetuses had significantly lower labelled cell indices for both alveolar epithelial cells and interstitial cells. These results indicate that pilocarpine treatment promotes differentiation of immature cells in the fetal lung at the expense of cell proliferation. 相似文献
3.
Trimetrexate for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome 总被引:12,自引:0,他引:12
C J Allegra B A Chabner C U Tuazon D Ogata-Arakaki B Baird J C Drake J T Simmons E E Lack J H Shelhamer F Balis 《The New England journal of medicine》1987,317(16):978-985
Preclinical studies have demonstrated that trimetrexate is a potent inhibitor of dihydrofolate reductase from Pneumocystis carinii. On the basis of this evidence, this lipid-soluble antifolate was used as an antipneumocystis agent in 49 patients with the acquired immunodeficiency syndrome (AIDS) and pneumocystis pneumonia. Simultaneous treatment with the reduced folate leucovorin was used as a specific antidote to protect host tissues from the toxic effects of the antifolate without affecting the antipneumocystis action of trimetrexate. Patients were assigned to three groups and treated for 21 days: in Group I, trimetrexate with leucovorin was used as salvage therapy in patients in whom standard treatments (both pentamidine isethionate and trimethoprim-sulfamethoxazole) could not be tolerated or had failed (16 patients); in Group II, trimetrexate with leucovorin was used as initial therapy in patients with a history of sulfonamide inefficacy or intolerance (16 patients); and in Group III, trimetrexate with leucovorin plus sulfadiazine was used as initial therapy (17 patients). The response and survival rates were, respectively, 69 percent and 69 percent in Group I; 63 percent and 88 percent in Group II; and 71 percent and 77 percent in Group III. Trimetrexate therapy had minimal toxicity; transient neutropenia or thrombocytopenia occurred in 12 patients and mild elevation of serum aminotransferases in 4. We conclude that the combination of trimetrexate and leucovorin is safe and effective for the initial treatment of pneumocystis pneumonia in patients with AIDS and for the treatment of patients with intolerance or lack of response to standard therapies. 相似文献
4.
Pharmacokinetics,cerebrospinal fluid penetration,and metabolism of piroxantrone in the Rhesus monkey
Stacey L. Berg Frank M. Balis Karen S. Godwin David G. Poplack 《Investigational new drugs》1993,11(4):255-261
Summary Piroxantrone is an anthrapyrazole derivative with broad anti-tumor activityin vitro and less cardiac toxicity than the anthracyclines. The metabolic pathways and central nervous system penetration of piroxantrone have not been determined. In this study we examined the pharmacokinetic behavior of piroxantrone in plasma and cerebrospinal fluid in a non-human primate model. In addition, a urinary metabolite of piroxantrone was isolated and its cytotoxicity evaluatedin vitro.
The disappearance of piroxantrone from plasma after an intravenous dose of 150 mg/m2 given over 60 minutes was biexponential with mean t1/2 alpha of 1.0 minutes and a mean t1/2 beta of 180 minutes. The mean area under the curve was 220 M·min and the clearance was 1420 ml/min/m2. Piroxantrone was not detectable in the cerebrospinal fluid.Piroxantrone and three other compounds not present in pre-treatment samples were detected in urine. The major urinary metabolite was isolated. Its cytotoxicity against MOLT-4 cellsin vitro was at least one log less than that of piroxantrone. In addition, one of the other compounds detected in urine was determined to be a glucuronide conjugation product of the major metabolite.The results of this study may be useful in the interpretation of the activity and toxicity of piroxantrone in clinical trials. 相似文献
5.
Phase I trial and pharmacokinetic study of BMS-247550, an epothilone B analog, administered intravenously on a daily schedule for five days. 总被引:4,自引:0,他引:4
Jame Abraham Manish Agrawal Susan Bakke Ann Rutt Maureen Edgerly Frank M Balis Brigitte Widemann Louis Davis Bharat Damle Daryl Sonnichsen David Lebwohl Susan Bates Herb Kotz Tito Fojo 《Journal of clinical oncology》2003,21(9):1866-1873
PURPOSE: The epothilones are a novel class of nontaxane microtubule-stabilizing agents. BMS-247550 is a semisynthetic analog of the natural product epothilone B. We conducted a phase I study administering BMS-247550 as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. PATIENTS AND METHODS: Twenty-one patients received BMS-247550 without filgrastim in the first cycle. An additional six patients were enrolled at a starting dose of 8 mg/m2/d with filgrastim support. Twenty-one of the 27 patients had received prior paclitaxel, docetaxel, or both. RESULTS: One hundred seven cycles were administered to 27 patients. The maximum-tolerated dose was 6 mg/m2 of BMS-247550 administered as a 1-hour intravenous infusion daily for 5 consecutive days every 21 days. Dose-limiting toxicity at a dose of 8 mg/m2/d was neutropenia with or without filgrastim support. Nonhematologic grade 3 toxicities included fatigue (seven cycles), stomatitis (two cycles), and anorexia (one cycle). The mean terminal half-life of BMS-247550 was 16.8 +/- 6.0 hours, the volume of distribution at steady-state was 798 +/- 375 L, and the clearance was 712 +/- 247 mL/min. Objective responses were observed in patients with breast, cervical, and basal cell cancer. Reductions in CA-125 levels were noted in patients with ovarian cancer. CONCLUSION: The recommended phase II dose of BMS-247550 on the daily schedule for 5 days is 6 mg/m2/d. Neutropenia was dose limiting, but higher doses were tolerated by a large fraction of patients with filgrastim support. Peripheral neuropathy was mild, even after multiple cycles of therapy, and was not dose limiting. 相似文献
6.
7.
Kathleen Neville Robert A Parise Patrick Thompson Alexander Aleksic Merrill J Egorin Frank M Balis Leticia McGuffey Cynthia McCully Stacey L Berg Susan M Blaney 《Clinical cancer research》2004,10(7):2525-2529
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 of imatinib in the treatment of malignant gliomas and other solid tumors is being evaluated. We used a nonhuman primate model that is highly predictive of the cerebrospinal fluid penetration of drugs in humans to study the pharmacokinetics of imatinib in plasma and cerebrospinal fluid (CSF) after i.v. and p.o. administration. EXPERIMENTAL DESIGN: Imatinib, 15 mg/kg i.v. over 30 min (n = 3) or 30 mg/kg p.o. (n = 3), was administered to nonhuman primates. Imatinib was measured in serial samples of plasma and CSF using high-pressure liquid chromatography with UV absorbance or mass spectroscopic detection. Pharmacokinetic parameters were estimated using model-independent methods. RESULTS: Peak plasma imatinib concentrations ranged from 6.4 to 9.5 microM after i.v. dosing and 0.8 to 2.8 microM after p.o. dosing. The mean +/-SD area under the plasma concentration versus time curve was 2480 +/-1340 microM.min and 1191 +/-146 microM.min after i.v. and p.o. dosing, respectively. The terminal half-life was 529 +/-167 min after i.v. dosing and 266 +/-88 min after p.o. dosing. After i.v. dosing the steady state volume of distribution was 5.9 +/-2.8 liter/kg, and the total body clearance was 12 +/-5 ml/min/kg. The mean peak CSF concentration was 0.25 +/-0.07 microM after i.v. dosing and 0.07 +/-0.04 microM after p.o. dosing. The mean CSF:plasma area under the plasma concentration versus time curve ratio for all of the animals was 5% +/-2%. CONCLUSIONS: There is limited penetration of imatinib into the CSF of nonhuman primates after i.v. and p.o. administration. 相似文献
8.
Ian H. de Boer Charles E. Alpers Evren U. Azeloglu Ulysses G.J. Balis Jonathan M. Barasch Laura Barisoni Kristina N. Blank Andrew S. Bomback Keith Brown Pierre C. Dagher Ashveena L. Dighe Michael T. Eadon Tarek M. El-Achkar Joseph P. Gaut Nir Hacohen Yongqun He Jeffrey B. Hodgin Sanjay Jain Sandy Alfano 《Kidney international》2021,99(3):498-510
9.
10.
Pharmacokinetics and metabolism of the methotrexate metabolite 2, 4-diamino-N(10)-methylpteroic acid
Widemann BC Sung E Anderson L Salzer WL Balis FM Monitjo KS McCully C Hawkins M Adamson PC 《The Journal of pharmacology and experimental therapeutics》2000,294(3):894-901
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 and delayed MTX excretion. DAMPA is eliminated more rapidly than MTX in these patients, suggesting nonrenal elimination. The pharmacokinetics and metabolism of DAMPA were studied in four nonhuman primates with reverse-phase HPLC with UV, photodiode array detection, and mass spectroscopy. The mean peak plasma DAMPA concentration was 51 microM and the plasma disposition was described by a three-compartment open model with first order elimination. The mean clearance of DAMPA was 1.9 l/kg/h and the mean terminal half-life was 51 min. Forty-six percent of the dose was excreted in the urine as parent compound. Three DAMPA metabolites, hydroxy-DAMPA, DAMPA-glucuronide, and hydroxy-DAMPA-glucuronide, were identified in plasma and urine. These metabolites also were identified in plasma from patients who received CPDG(2) as an MTX rescue agent. The cytotoxicity of DAMPA and its effect on MTX cytotoxicity were assessed in the Molt-4 human leukemic cell line. DAMPA was not cytotoxic and did not significantly alter the cytotoxicity of MTX. In nonhuman primates metabolism of DAMPA is a major route of DAMPA elimination, and metabolism underlies the more rapid elimination of DAMPA versus MTX in patients with MTX-induced renal dysfunction after administration of CPDG(2). 相似文献