NRL972(NRL972) - _专利_临床

概要

基本信息

药物类型

小分子化药

别名

Cholyl-lysyl-fluorescein、Fluorescein Lisicol

靶点-

作用机制-

治疗领域

消化系统疾病感染其他疾病

在研适应症-

非在研适应症

慢性肝病慢性病毒性肝炎纤维化+ [3]

原研机构

诺金有限公司

在研机构-

非在研机构

Norgine Ltd.

最高研发阶段无进展临床3期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C51H63N3O11S

InChIKeyKHNJPPGHIWPDLG-DXNXUNFASA-N

CAS号140616-46-2

关联

11

项与 NRL972 相关的临床试验

NCT00896597 / Completed临床1期

An Open, Randomised Study to Compare the Reproducibility of CTP Rating and NRL972 Pharmacokinetics in Patient Volunteers With Hepatic Cirrhosis.

This is an open, randomized study in patients with different severity stages of hepatic cirrhosis, in which rater pairs will be used for the assessment of the intra- and inter-rater reproducibility of NRL972 pharmacokinetics and CTP sum score. Rating will be performed by 32 to 40 pairs of raters. The raters will perform the required assessments in the capacity of sub-investigators of the phase I (co-ordinating) unit.
Up to 240 patients with clinically established hepatic cirrhosis without confounding end-stage co-morbidity (stable disease) will be studied. Within 30 days of confirmation of eligibility, Visit 1 will take place to determine the investigational parameters (NRL972 pharmacokinetics, clinical laboratory tests, and determination of CTP sum score). At approximate intervals of one week, Visits 2, 3 and 4 will occur, and the investigational parameters will again be assessed.

开始日期2009-04-01

申办/合作机构

Norgine Ltd.

NCT00915057 / Completed临床2期

An Open Study to Investigate the Effects of Chronic Viral Hepatitis B or C on the Pharmacokinetics of Cholyl-lysyl-fluorescein (NRL972) Before, During and After Standard Treatment.

Little is known about the nature and extent of the disturbance in hepatic function and biliary hepatic clearance in chronic viral hepatitis, while the course of this disease, the functional implications and response to treatment are difficult to predict. This study aims to assess this in patients with chronic viral hepatitis B (CHB) and chronic viral hepatitis C (CHC) who are eligible for treatment in accordance with the established consensus guidelines in the involved countries. The pharmacokinetics of NRL972 will be determined at baseline (within one month of starting treatment), at 3-monthly intervals during treatment, for up to 12 months (or at the end of treatment), and at 3 and 6 months after the end on treatment. This will provide a clearer understanding regarding the use of the pharmacokinetics of NRL972 in detecting changes in biliary clearance during and after treatment for CHB and CHC.

开始日期2009-03-01

申办/合作机构

Norgine Ltd.

EUCTR2008-003547-36-BG / Not yet recruitingN/A

An open study to investigate the effects of chronic hepatitis B or C on the pharmacokinetics of cholyl-lysyl-fluorescein (NRL972) before, during and after standard treatment - NRL972 in chronic heptatitis

开始日期2009-02-12

申办/合作机构

Norgine Ltd.

100 项与 NRL972 相关的临床结果

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100 项与 NRL972 相关的转化医学

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100 项与 NRL972 相关的专利（医药）

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3

项与 NRL972 相关的文献（医药）

2015-07-01·Int. Journal of Clinical Pharmacology and Therapeutics4区 · 医学

Effects of renal insufficiency on the elimination of fluorescein lisicol (NRL972), an investigational marker of hepatic transporter function

4区 · 医学

Article

作者: Deliyska, Boriana ; de Mey, Christian ; Gatchev, Emil

BACKGROUNDNRL972 (Fluorescein Lisicol), a fluorescent-labelled bile salt, is an investigational marker of hepatic biliary transporter function.OBJECTIVETo investigate the pharmacokinetics (PK) of NRL972 in patients with severe (SRI: creatinine clearance (CLCr)<30 mL/min per 1.73 m2 body surface area (BSA)) and mild-to-moderate renal insufficiency (MRI: 30≤CLCr<80 mL/min) relative to matched controls (CON: CLCr≥90 mL/min).METHODSThe plasma and urinary PK of NRL972 were determined after single 2-mg doses of NRL972 administered by 15-second intravenous (IV) injection. The PK were derived noncompartmentally using all data points up to 6 hours after dosing or only using the concentrations at 10 and 30 minutes after injection.RESULTS17, 22, and 16 subjects were enrolled in the SRI, MRI, and CON group, respectively. NRL972 was hardly quantifiable in urine in any of the subjects groups. The plasma concentrations of NRL972 declined rapidly after dosing in mostly monoexponential fashion. The decline tended to be faster in patients with renal insufficiency: in SRI patients, the point and 95% confidence interval (CI) estimates of the group ratios (SRI/CON) were 0.691 (CI: 0.517 to 0.925) for the C(30):C(10) concentration ratio, 0.785 (CI: 0.634 to 0.970) for t1/2, and 1.344 (CI: 1.028 to 1.757) for bodyweight normalized clearance (CL/BW); in MRI patients, the effect was slightly less.CONCLUSIONRenal insufficiency does not impair the elimination of NRL972; instead, there is a trend of enhanced NRL972 disposition in patients with compromised renal function. Concomitant renal impairment is unlikely to have confounding effects on the evaluation of hepatic function by NRL972 testing.

1995-06-01·Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism

Biliary lipid output by isolated perfused rat livers in response to cholyl-lysylfluorescein

Article

作者: David Billington ; Elwyn Elias ; Khalid Rahman ; Charles O. Mills ; Alison J. Bushell ; Debbie J. Baxter

The biliary output of bile acids and lipids is tightly coupled. The ability of the natural bile acid glycocholate to trigger biliary lipid secretion was compared with that of the fluorescent bile acid analogue cholyl-lysylfluorescein (cholyl-lys-F). When administered as a 5 min pulse of 2.5 mumol/min to bile acid-depleted rat livers perfused under recycling conditions, glycocholate produced well-defined peaks of phospholipid and cholesterol output, and of bile flow, which were coincident with the peak of bile acid output. Although cholyl-lys-F did trigger biliary lipid secretion, its time course of appearance was delayed and well-defined peaks of output were not observed. However, the increased biliary output of phospholipid and cholesterol was coincident with that of bile acids and, as judged by phospholipid/bile acid and cholesterol/bile acid ratios, cholyl-lys-F was as effective as glycocholate in triggering biliary lipid output. When administered to livers perfused under single pass conditions, perfusate to bile transfer of glycocholate was > 85% at infusion rates of up to 5 mumol/min whereas transfer of cholyl-lys-F showed saturation at infusion rates of > 0.2 mumol/min; the time course of biliary output of both bile acids was similar. Thus, under recycling conditions, cholyl-lys-F not taken up during first pass will be continually represented for transfer to bile, explaining why bile acid and lipid output did not occur as well-defined peaks.

1991-12-01·Biochimica et Biophysica Acta (BBA) - General Subjects

Cholyl-lysylfluorescein: synthesis, biliary excretion in vivo and during single-pass perfusion of isolated perfused rat liver

Article

作者: E. Elias ; R. Coleman ; C.O. Mills ; K. Rahman

A fluorescent bile salt, cholyl-lysylfluorescein (cholyl-lys-F), was synthesised so that it retained both an intact steroid ring and a side chain structure with an unblocked carboxyl group. Its biliary kinetics and hepatic extraction were studied in Wistar rats and in the isolated perfused rat liver, respectively. The synthetic method used excess N-epsilon-CBZ-l-lysine methyl ester hydrochloride (7 mmol) and cholic acid (5 mmol) via EEDQ with a yield of 94% for cholyl-lys. Cholyl-lys-F was synthesized employing equimolar amounts of cholyl-lys (sodium salt) and fluorescein isothiocyanate (FITC) in bicarbonate buffer (pH 9.5) over 16 h at room temperature (21 degrees C) with a yield of 70%. The fluorescent property of cholyl-lys-F was similar to fluorescein with a strong apple-green fluorescence. In bile-fistula rats under pentobarbital anaesthesia, the cumulative 20 min biliary excretion as a percentage of injected dose were as follows: cholyl-lys-F, 94.4 +/- 0.3%, [14C]cholylglycine (CG), 93.1 +/- 1.2% and fluorescein (F), 34.8 +/- 0.5. Furthermore the single-pass hepatic extraction of cholyl-lys-F was 64.1 +/- 3.9%, [14C]CG was 66.1 +/- 1.2% and F was 16.5 +/- 2%. The similarity in biliary output and hepatic extraction of cholyl-lys-F to that of the natural bile acid cholylglycine suggest that both compounds are handled in a similar fashion. The greater biliary excretion and hepatic extraction of cholyl-lys-F relative to free fluorescein further suggest that conjugation with a bile salt may be an efficient way of targeting compounds to the liver.

100 项与 NRL972 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性病毒性肝炎	临床3期	罗马尼亚	Norgine Ltd.	2009-03-01
慢性病毒性肝炎	临床3期	保加利亚	Norgine Ltd.	2009-03-01
慢性丙型肝炎	临床3期	罗马尼亚	Norgine Ltd.	2009-03-01
慢性丙型肝炎	临床3期	保加利亚	Norgine Ltd.	2009-03-01
非酒精性脂肪性肝炎	临床3期	美国	Norgine Ltd.	2008-06-01
纤维化	临床3期	德国	Norgine Ltd.	2008-03-01
肝硬化	临床3期	德国	Norgine Ltd.	2008-03-01
慢性肝病	临床3期	保加利亚	Norgine Ltd.	2004-08-01