当前位置： SCI文献检索 > INVESTIGATIONAL NEW DRUGS期刊下所有文献 > Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.

Distribution, elimination, metabolism and bioavailability of hexamethylenebisacetamide in rats.

Abstract：

:Hexamethylenebisacetamide (HMBA), an in vitro differentiating agent, was studied for its pharmacodynamic actions in animals. Plasma stability, organ distribution, excretion, oral bioavailability, and estimates of pharmacokinetic parameters and acute lethality were determined in rats. The single dose intraperitoneal LD50 was greater than 3000 mg/kg in both mice and rats. The drug was stable in plasma from several different species during an 8 h in vitro incubation at 37 degrees C. Following a single intravenous (iv) bolus injection (1000 mg/kg) to rats, HMBA was removed from the plasma with a half time of 2.2 +/- 0.5 h, and 65 +/- 8% of the dose was excreted unchanged in the urine during the first 24 h after dosing. During an 8 h iv infusion, plasma concentrations of 4 mM were easily maintained with no apparent adverse effects. Drug was uniformly distributed, with highest concentrations found in thymus, kidney, liver, and lymph node throughout the first 24 h after a single iv bolus dose. In vivo metabolism was very small, and the presence of apparent metabolites was undetectable until 48 h after iv administration. Oral bioavailability was good (32%), with peak plasma concentrations of 2 mM achieved one hour after oral administration. After oral dosing urinary excretion and plasma decay were comparable to similar data obtained after iv dosing.

journal_name

Invest New Drugs

journal_title

Investigational new drugs

authors

Litterst CL,Roth JS,Kelley JA

doi

10.1007/BF00179430

subject

Has Abstract

pub_date

1985-01-01 00:00:00

pages

263-72

issue

3

eissn

0167-6997

issn

1573-0646

journal_volume

3

pub_type

杂志文章

相关文献

INVESTIGATIONAL NEW DRUGS文献大全
  • Phase I study of weekly plitidepsin as 1-hour infusion combined with carboplatin in patients with advanced solid tumors or lymphomas.

    abstract：:This dose-escalating phase I clinical trial was designed to determine the recommended dose (RD) and to assess the safety and feasibility of weekly plitidepsin (1-hour i.v. infusion, Days 1, 8 and 15) combined with carboplatin (1-hour i.v. infusion, Day 1, after plitidepsin) in 4-week (q4wk) cycles given to patients wi...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-010-9488-1

    authors： Salazar R,Plummer R,Oaknin A,Robinson A,Pardo B,Soto-Matos A,Yovine A,Szyldergemajn S,Calvert AH

    更新日期：2011-12-01 00:00:00

  • Phase II trial of intravenous melphalan for metastatic colorectal carcinoma. A Southwest Oncology Group study.

    abstract：:Based on the high response rates seen among patients with colon cancer receiving high dose Melphalan with autologous marrow infusion, the Southwest Oncology Group conducted a Phase II trial of the compound at a conventional dose. The initial starting dose of 40 mg/m2 was reduced to 30 mg/m2 after severe myelotoxicity ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00171991

    authors： Knight WA 3rd,Goodman P,Taylor SA,Macdonald JS,Coltman CA Jr,Constanzi JJ,Baker LH

    更新日期：1990-01-01 00:00:00

  • Phase II study of gemcitabine for treatment of patients with advanced stage marginal zone B-cell lymphoma: Consortium for Improving Survival of Lymphoma (CISL) trial.

    abstract：BACKGROUND:Therapeutic approaches to marginal zone B-cell lymphoma (MZL) continue to evolve. Localized MZL responds favorably to local treatments, including surgery and/or local radiation therapy. However, MZL manifests as a disseminated disease in one-third of the cases at diagnosis. Moreover, relapses involving dista...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究

    doi：10.1007/s10637-009-9260-6

    authors： Oh SY,Kim WS,Lee DH,Kim SJ,Kim SH,Ryoo BY,Kang HJ,Choi YJ,Chung JS,Kim HJ,Suh C

    更新日期：2010-04-01 00:00:00

  • Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel.

    abstract：:The population approach has been implemented prospectively in the clinical development of docetaxel (Taxotere). Overall 640 patients were evaluable for the population PK/PD analysis. The PK analysis evidenced significant covariates explaining the inter-patient variability of docetaxel clearance and the PK/PD analysis ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1023/a:1010687017717

    authors： Bruno R,Vivier N,Veyrat-Follet C,Montay G,Rhodes GR

    更新日期：2001-05-01 00:00:00

  • A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma.

    abstract：BACKGROUND:Hepatocellular carcinoma (HCC) cells are auxotrophic for arginine, depletion of which leads to tumour regression. The current study evaluated safety, pharmacokinetics (PK)/ pharmacodynamics (PD) parameters, and potential anti-tumor activity of pegylated recombinant human arginase 1 (peg-rhArg1) in advanced H...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-012-9807-9

    authors： Yau T,Cheng PN,Chan P,Chan W,Chen L,Yuen J,Pang R,Fan ST,Poon RT

    更新日期：2013-02-01 00:00:00

  • Phase II trial of ifosfamide in epidermoid carcinoma of the esophagus: unexpectant severe toxicity.

    abstract：:Thirty-two patients with advanced epidermoid carcinoma of the esophagus were treated with ifosfamide (1.50 gm/m2 daily x 5 days) with uroprotective mesna in a phase II study. Eighteen patients were previously untreated. Of 28 evaluable patients, two (7%) had partial remissions lasting 2+ and 6+ months. Toxicity was pr...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00175406

    authors： Nanus DM,Kelsen DP,Lipperman R,Eisenberger M

    更新日期：1988-09-01 00:00:00

  • Developmental antiangiogenic agents for the treatment of non-small cell lung cancer (NSCLC).

    abstract：:Standard therapy for advanced or metastatic non-small cell lung cancer (NSCLC) has primarily consisted of traditional cytotoxic chemotherapy, although use of targeted therapies has been approved in specific settings. Antiangiogenic agents represent a promising therapeutic strategy for treatment of advanced NSCLC. Beva...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,评审

    doi：10.1007/s10637-011-9750-1

    authors： Blumenschein GR Jr

    更新日期：2012-08-01 00:00:00

  • Tetra-O-methyl nordihydroguaiaretic acid, an inhibitor of Sp1-mediated survivin transcription, induces apoptosis and acts synergistically with chemo-radiotherapy in glioblastoma cells.

    abstract：:Glioblastoma (GBM), one of the most malignant human neoplasias, responds poorly to current treatment modalities, with temozolomide (TMZ) being the drug most frequently used for its treatment. Tetra-O-methyl Nordihydroguaiaretic Acid (M4N) is a global transcriptional repressor of genes dependent on the Sp1 transcriptio...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-012-9917-4

    authors： Castro-Gamero AM,Borges KS,Moreno DA,Suazo VK,Fujinami MM,de Paula Gomes Queiroz R,de Oliveira HF,Carlotti CG Jr,Scrideli CA,Tone LG

    更新日期：2013-08-01 00:00:00

  • A phase II trial of diaziquone (AZQ) in mixed mesodermal sarcomas of the uterus. A Gynecologic Oncology Group study.

    abstract：:AZQ was given intravenously to 23 patients with mixed mesodermal sarcoma of the uterus refractory to conventional treatment at a dose of 22.5-30 mg/m2 q three weeks. There was one partial response lasting seven weeks and one drug-related death. Based upon the activity observed in this trial, there does not appear to b...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章,多中心研究

    doi：10.1007/BF00194555

    authors： Slayton RE,Blessing JA,Clarke-Pearson D

    更新日期：1991-02-01 00:00:00

  • Restricted brain penetration of the tyrosine kinase inhibitor erlotinib due to the drug transporters P-gp and BCRP.

    abstract：PURPOSE:Erlotinib (Tarceva®, OSI-774) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. As high-grade gliomas frequently show amplification, overexpression and/or mutation of EGFR, this drug has been tested in several clinical trials with glioblastoma patients, but unfortunat...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-010-9569-1

    authors： de Vries NA,Buckle T,Zhao J,Beijnen JH,Schellens JH,van Tellingen O

    更新日期：2012-04-01 00:00:00

  • Phase II trial of low-dose N-(phosphonacetyl)-disodium L-aspartic acid and high-dose 24-hour infusional 5-fluorouracil in advanced gastric adenocarcinoma. A Southwest Oncology Group study.

    abstract：:N-(phosphonacetyl)-disodium L-aspartic acid (PALA) demonstrates a synergistic antitumor effect when combined with 5-Fluorouracil (5-FU) in in vitro studies. In a Phase II trial, 23 eligible patients with unresectable or metastatic adenocarcinoma of the stomach were treated with weekly i.v. bolus PALA (250 mg/M2) follo...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1007/BF00180821

    authors： Martino RL,Fleming TR,Morrell LM,Ardalan B,Richman SP,Macdonald JS

    更新日期：1996-01-01 00:00:00

  • Plasma and cerebrospinal fluid pharmacokinetics of vincristine and vincristine sulfate liposomes injection (VSLI, marqibo®) after intravenous administration in Non-human primates.

    abstract：PURPOSE:Vincristine sulfate liposomes injection (VSLI, Marqibo®) is an FDA approved encapsulated preparation of standard vincristine in sphingomyelin/cholesterol liposomes. Clinical pharmacokinetics show VSLI to be a long-circulating, slow release formulation that is confined to plasma, and prior data on cerebrospinal ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-015-0311-x

    authors： Shah NN,Cole DE,Lester-McCully CM,Wayne AS,Warren KE,Widemann BC

    更新日期：2016-02-01 00:00:00

  • Synergistic effects of the combination of β-ionone and sorafenib on metastasis of human hepatoma SK-Hep-1 cells.

    abstract：:The combination of anti-cancer drugs with nutritional factors is a potential strategy for improving the efficacy of chemotherapy, particularly for hepatocellular carcinoma because its conventional therapies are mostly ineffective. Using a highly invasive hepatoma SK-Hep-1 cell line, we investigated the possible synerg...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-011-9727-0

    authors： Huang CS,Lyu SC,Hu ML

    更新日期：2012-08-01 00:00:00

  • A phase I study of everolimus and CHOP in newly diagnosed peripheral T-cell lymphomas.

    abstract：BACKGROUND:We performed a phase I study to determine the dose and safety of everolimus as a combination chemotherapy in peripheral T-cell lymphoma (PTCL). METHODS:Four dose levels (2.5 to 10 mg) of everolimus from days 1 to 14 with CHOP (750 mg/m(2) cyclophosphamide, 50 mg/m(2) doxorubicin, and 1.4 mg/m(2) (maximum 2 ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-013-0015-z

    authors： Kim SJ,Kang HJ,Kim JS,Eom HS,Huh J,Ko YH,Lee J,Yim DS,Lee SY,Park WS,Yang WI,Lee SS,Suh C,Kim WS

    更新日期：2013-12-01 00:00:00

  • AN-7, a butyric acid prodrug, sensitizes cutaneous T-cell lymphoma cell lines to doxorubicin via inhibition of DNA double strand breaks repair.

    abstract：:We previously found that the novel histone deacetylase inhibitor (HDACI) butyroyloxymethyl diethylphosphate (AN-7) had greater selectivity against cutaneous T-cell lymphoma (CTCL) than SAHA. AN-7 synergizes with doxorubicin (Dox), an anthracycline antibiotic that induces DNA breaks. This study aimed to elucidate the m...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-017-0500-x

    authors： Moyal L,Goldfeiz N,Gorovitz B,Rephaeli A,Tal E,Tarasenko N,Nudelman A,Ziv Y,Hodak E

    更新日期：2018-02-01 00:00:00

  • Using the neurotransmitter serotonin to target imaging agents to glioblastoma cells.

    abstract：:The neurotransmitter serotonin is involved in numerous bodily functions via seven different serotonin receptor subfamilies. Serotonin plays a role in gastrointestinal functions like intestinal secretion or peristalsis and neuropsychiatric events like depression or migraine. One of these subtypes has been found on glio...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-011-9781-7

    authors： Sturzu A,Sheikh S,Klose U,Echner H,Kalbacher H,Deeg M,Nägele T,Horger M,Ernemann U,Heckl S

    更新日期：2012-12-01 00:00:00

  • First-line combination chemotherapy with mitoxantrone and cyclophosphamide in advanced breast cancer.

    abstract：:In this study, 30 evaluable patients with advanced carcinoma of the breast were treated with cyclophosphamide 600 mg/m2 i.v. followed one day later with mitoxantrone (Novantrone; dihydroxyanthracenedione) 16 mg/m2 i.v. Drug treatment was repeated every 3-4 weeks, for a maximum of 12 cycles. The overall response rate w...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00174165

    authors： Periti P,della Cuna GR,Pannuti F,Mazzei T,Preti P,Martoni A,Mini E

    更新日期：1985-01-01 00:00:00

  • Pharmacokinetic and phase I studies of brequinar (DUP 785; NSC 368390) in combination with cisplatin in patients with advanced malignancies.

    abstract：:Brequinar (DUP 785; NSC 368390) is a quinoline carboxylic acid derivative that inhibits pyrimidine synthesis at the level of dihydro-orotate dehydrogenase and revealed synergy with cisplatin in preclinical models. In this study investigating the pharmacokinetic and toxicity of brequinar in combination with cisplatin, ...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1023/a:1016066529642

    authors： Burris HA 3rd,Raymond E,Awada A,Kuhn JG,O'Rourke TJ,Brentzel J,Lynch W,King SY,Brown TD,Von Hoff DD

    更新日期：1998-01-01 00:00:00

  • In vitro antitumor effect of recombinant human tumor necrotizing factor on cultured human cancer cell lines and freshly isolated lung cancer cells by the human tumor clonogenic assay.

    abstract：:In vitro antitumor effects of human recombinant tumor necrotizing factor (rH-TNF) were examined against nine lung cancer cell lines including six non small and three small cell lung cancer, four stomach cancer cell lines and 30 freshly isolated lung cancer cell samples by the human tumor clonogenic assay. rH-TNF did n...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00169974

    authors： Sasaki Y,Kanzawa F,Takahashi H,Matsushima Y,Nakano H,Nakagawa K,Hong WS,Minato K,Fujiwara Y,Saijo N

    更新日期：1987-12-01 00:00:00

  • Structure-activity relationships between the Aconitum C20-diterpenoid alkaloid derivatives and the growth suppressive activities of Non-Hodgkin's lymphoma Raji cells and human hematopoietic stem/progenitor cells.

    abstract：:The anti-tumor properties of novel derivatives prepared from Aconitum C(20)-diterpenoid alkaloid, which show the least toxicity among the Aconitum alkaloids, were investigated in the Non-Hodgkin's lymphoma cell line Raji cells. Two novel Aconitum C(20)-diterpenoid alkaloid derivatives, 11-m-Trifluorometylbenzoyl (Mb)-...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-009-9327-4

    authors： Hazawa M,Takahashi K,Wada K,Mori T,Kawahara N,Kashiwakura I

    更新日期：2011-02-01 00:00:00

  • Predictive factors for response to treatment in patients with advanced renal cell carcinoma.

    abstract：INTRODUCTION:The analysis of predictive factors of response may aid in predicting which patients with advanced renal cell carcinoma (RCC) would be good candidates for systemic treatments. MATERIALS AND METHODS:The expression of several biomarkers was retrospectively analyzed using immunohistochemistry (IHC), as well a...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-012-9836-4

    authors： Muriel López C,Esteban E,Astudillo A,Pardo P,Berros JP,Izquierdo M,Crespo G,Fonseca PJ,Sanmamed M,Martínez-Camblor P

    更新日期：2012-12-01 00:00:00

  • Phase I study of matuzumab in combination with 5-fluorouracil, leucovorin and cisplatin (PLF) in patients with advanced gastric and esophagogastric adenocarcinomas.

    abstract：BACKGROUND:To evaluate the safety and tolerability of two different weekly doses of the fully humanized epidermal growth factor receptor (EGFR)-targeting monoclonal antibody matuzumab combined with high-dose 5-fluorouracil, leucovorin and cisplatin (PLF) in the first-line treatment of patients with EGFR-positive advanc...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-012-9848-0

    authors： Trarbach T,Przyborek M,Schleucher N,Heeger S,Lüpfert C,Vanhoefer U

    更新日期：2013-06-01 00:00:00

  • Phase I study of Tomudex and Doxorubicin in patients with locally advanced, inoperable or metastatic cancer (IND.98).

    abstract：BACKGROUND:The primary objective of this Phase I study was to determine the maximum tolerated dose (MTD) and recommended phase II dose for Tomudex and Doxorubicin when given in combination to patients with advanced metastatic cancer. The secondary objective was to assess the toxicity profile. PATIENTS AND METHODS:Star...

    journal_title：Investigational new drugs

    pub_type： 临床试验,杂志文章

    doi：10.1023/B:DRUG.0000047105.38511.2a

    authors： Bjarnason GA,Charpentier D,Wong R,Goel R,Douglas L,Walsh W,Matthews S,Dent S,Seymour L,Winquist E

    更新日期：2005-01-01 00:00:00

  • Phase I/II study of erlotinib plus S-1 for patients with previously treated non-small cell lung cancer: Thoracic Oncology Research Group (TORG) 0808/0913.

    abstract：:Introduction In preclinical data, the combination therapy with S-1 and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) had a synergistic antitumor effect on non-small cell lung cancer (NSCLC), regardless of the EGFR mutation status. Patients and Methods Patients with previously treated NSCLC an...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-020-00985-4

    authors： Nakahara Y,Shimokawa T,Misumi Y,Nogami N,Shinkai T,Seki N,Hosomi Y,Hida N,Okamoto H

    更新日期：2020-08-15 00:00:00

  • INNO-206, the (6-maleimidocaproyl hydrazone derivative of doxorubicin), shows superior antitumor efficacy compared to doxorubicin in different tumor xenograft models and in an orthotopic pancreas carcinoma model.

    abstract：:The (6-maleimidocaproyl)hydrazone derivative of doxorubicin (INNO-206) is an albumin-binding prodrug of doxorubicin with acid-sensitive properties that is being assessed clinically. The prodrug binds rapidly to circulating serum albumin and releases doxorubicin selectively at the tumor site. This novel mechanism may p...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-008-9208-2

    authors： Graeser R,Esser N,Unger H,Fichtner I,Zhu A,Unger C,Kratz F

    更新日期：2010-02-01 00:00:00

  • Osimertinib for patients with poor performance status and EGFR T790M mutation-positive advanced non-small cell lung cancer: a phase II clinical trial.

    abstract：:Osimertinib is a molecularly targeted agent used to treat non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) T790M mutation. However, its efficacy and safety profile when patients have poor performance status (PS) is unknown. Therefore, we conducted an open-label, multi-center,...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-020-00943-0

    authors： Nakashima K,Ozawa Y,Daga H,Imai H,Tamiya M,Tokito T,Kawamura T,Akamatsu H,Tsuboguchi Y,Takahashi T,Yamamoto N,Mori K,Murakami H

    更新日期：2020-12-01 00:00:00

  • Absolute and relative activities of platinum-complexes on human tumors as evaluated by an antimetabolic in vitro assay.

    abstract：:An in vitro assay, which evaluates drug effect on 3H-thymidine incorporation, was used to investigate the absolute and relative activities of cisplatin (DDP), carboplatin (CBDCA) and iproplatin (CHIP) on 317 specimens from untreated tumors, including breast and ovarian cancers and malignant melanomas. Similar activiti...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/BF00175294

    authors： Daidone MG,Silvestrini R,Zaffaroni N,Grignolio E,Landoni F

    更新日期：1987-01-01 00:00:00

  • Inhibition of cell growth, induction of apoptosis and mechanism of action of the novel platinum compound cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate.

    abstract：:Cis-diaminechloro-[2-(diethylamino) ethyl 4-amino-benzoate, N(4)]-chloride platinum (II) monohydrochloride monohydrate (DPR) is a new platinum triamine complex obtained from the synthesis of cisplatin and procaine. In this paper we analyzed, adopting a disease-oriented strategy, the tumour selectivity of this compound...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1023/b:drug.0000006170.38419.c9

    authors： Mariggiò MA,Cafaggi S,Ottone M,Parodi B,Vannozzi MO,Mandys V,Viale M

    更新日期：2004-01-01 00:00:00

  • Phase I study of oral CP-4126, a gemcitabine derivative, in patients with advanced solid tumors.

    abstract：:CP-4126 is a gemcitabine (2',2'-difluorodeoxycytidine; dFdC) 5' elaidic acid ester. The purpose of this dose-escalating study was to assess safety, pharmacokinetics (PK) and preliminary antitumor activity of the oral formulation and to determine the recommended dose (RD) for phase II studies. The study had a two-step ...

    journal_title：Investigational new drugs

    pub_type： 杂志文章,多中心研究,随机对照试验

    doi：10.1007/s10637-013-9925-z

    authors： Stuurman FE,Voest EE,Awada A,Witteveen PO,Bergeland T,Hals PA,Rasch W,Schellens JH,Hendlisz A

    更新日期：2013-08-01 00:00:00

  • Two-stage model-based clinical trial design to optimize phase I development of novel anticancer agents.

    abstract：BACKGROUND:The phase I program of anticancer agents usually consists of multiple dose escalation studies to select a safe dose for various administration schedules. We hypothesized that pharmacokinetic and pharmacodynamic (PK-PD) modeling of an initial phase I study (stage 1) can be used for selection of an optimal sta...

    journal_title：Investigational new drugs

    pub_type： 杂志文章

    doi：10.1007/s10637-008-9216-2

    authors： Zandvliet AS,Karlsson MO,Schellens JH,Copalu W,Beijnen JH,Huitema AD

    更新日期：2010-02-01 00:00:00