Delving into the Latest Updates on Lamivudine/Zidovudine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Lamivudine/zidovudine (Mylan Pharmaceuticals), Lamuzid, Zidovudine and Lamivudine

+ [7]

Target

RT

Mechanism

RT inhibitors(Reverse transcriptase inhibitors)

Therapeutic Areas

Immune System DiseasesInfectious DiseasesUrogenital Diseases

Active Indication

HIV Infections

Inactive Indication-

Originator Organization

ViiV Healthcare Ltd.

Active Organization

ViiV Healthcare BV

ViiV Healthcare Ltd.

Inactive Organization

ViiV Healthcare Co.Pharmacare Ltd.Teva Pharmaceuticals Europe BV

Drug Highest PhaseApproved

First Approval Date

US (26 Sep 1997),

HIV Infections

RegulationPriority Review (CN)

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Structure

Molecular FormulaC10H13N5O4

InChIKeyHBOMLICNUCNMMY-XLPZGREQSA-N

CAS Registry30516-87-1

View All Structures (2)

主要研究目的：按有关生物等效性试验的规定，选择生产商为GlaxoSmithKline的齐多拉米双夫定片（商品名：Combivir®，规格：每片含齐多夫定300mg和拉米夫定150mg）为参比制剂，对安徽贝克生物制药有限公司生产并提供的受试制剂齐多拉米双夫定片（规格：每片含齐多夫定300mg和拉米夫定150mg）进行空腹和餐后给药人体生物等效性试验，比较受试制剂中药物的吸收速度和吸收程度与参比制剂的差异是否在可接受的范围内，评价两种制剂在空腹和餐后给药条件下的生物等效性。次要研究目的：观察健康志愿受试者口服受试制剂齐多拉米双夫定片（规格：每片含齐多夫定300mg和拉米夫定150mg）和参比制剂齐多拉米双夫定片（商品名：Combivir®，规格：每片含齐多夫定300mg和拉米夫定150mg）的安全性。

[Translation]

Main research purpose: According to the relevant provisions of bioequivalence test, the zidovudine tablets (trade name: Combivir®, specification: each tablet contains 300 mg of zidovudine and 150 mg of lamivudine) produced by GlaxoSmithKline were selected as the reference preparation, and the test preparation zidovudine tablets (specification: each tablet contains 300 mg of zidovudine and 150 mg of lamivudine) produced and provided by Anhui Baker Biopharmaceutical Co., Ltd. were subjected to fasting and postprandial human bioequivalence test, to compare whether the absorption rate and degree of the drug in the test preparation are within the acceptable range with the reference preparation, and to evaluate the bioequivalence of the two preparations under fasting and postprandial administration conditions. Secondary study objective: To observe the safety of oral administration of the test preparation Zidovudine Tablets (specification: each tablet contains 300 mg of zidovudine and 150 mg of lamivudine) and the reference preparation Zidovudine Tablets (trade name: Combivir®, specification: each tablet contains 300 mg of zidovudine and 150 mg of lamivudine) to healthy volunteers.

Start Date04 Nov 2022

Sponsor / Collaborator

Anhui Baker Biopharmaceutical Co., Ltd.

CTR20192017 / Completed

齐多拉米双夫定片在中国健康受试者单次、空腹及餐后、随机开放、两制剂、三周期三序列三交叉生物等效性试验

[Translation] A single-dose, fasting and postprandial, randomized, open-label, two-dose, three-period, three-sequence, three-crossover bioequivalence study of zidovudine tablets in healthy Chinese subjects

评价东北制药集团沈阳第一制药有限公司生产的齐多拉米双夫定片（规格：每片含齐多夫定300mg和拉米夫定150mg）与葛兰素史克制药公司生产的齐多拉米双夫定片（商品名：双汰芝®，规格：每片含齐多夫定300mg和拉米夫定150mg）的生物等效性。通过不良事件发生率、实验室检验结果、生命体征和体格检查的变化情况评估齐多拉米双夫定片安全性。

[Translation]

Evaluate the difference between Zidovudine tablets produced by Shenyang First Pharmaceutical Co., Ltd. of the Northeast Pharmaceutical Group (specifications: each tablet contains 300 mg of Zidovudine and 150 mg of Lamivudine) and Zidovudine produced by GlaxoSmithKline Pharmaceutical Company. Bioequivalence of Mildoudine Tablets (trade name: Shuangtaizhi®, specifications: each tablet contains 300 mg of zidovudine and 150 mg of lamivudine). The safety of Zidoramibivudine Tablets was evaluated through the incidence of adverse events, laboratory test results, changes in vital signs and physical examination.

Start Date03 Nov 2019

Sponsor / Collaborator

Dongbei Pharmaceutical Group Co. Shenyang No 1 Pharm Co. Ltd.

CTR20190551 / Suspended

齐多拉米双夫定片在中国健康受试者中随机、开放、空腹及餐后、单剂量、两周期、双交叉生物等效性试验

[Translation] A randomized, open-label, fasting and fed, single-dose, two-period, double-crossover bioequivalence study of zidovudine tablets in healthy Chinese subjects

比较受试制剂中药物的吸收程度和吸收速度与参比制剂的差异是否在可接受的范围内，比较两种制剂在空腹及餐后给药条件下的生物等效性。观察健康志愿受试者口服受试制剂齐多拉米双夫定片（规格：每片含拉米夫定150mg和齐多夫定300mg）和参比制剂齐多拉米双夫定片（商品名：双汰芝®，规格：每片含拉米夫定150mg和齐多夫定300mg）的安全性。

[Translation]

Compare whether the absorption degree and absorption rate of the drug in the test preparation are within the acceptable range with the reference preparation, and compare the bioequivalence of the two preparations under fasting and postprandial administration conditions. Observe the safety of healthy volunteers taking the test preparation Zidovudine Tablets (Specifications: Each tablet contains 150 mg of lamivudine and 300 mg of zidovudine) and the reference preparation Zidovudine Tablets (trade name: Shuangtaizhi®, specifications: Each tablet contains 150 mg of lamivudine and 300 mg of zidovudine).

Start Date19 Apr 2019

Sponsor / Collaborator

Anhui Baker Biopharmaceutical Co., Ltd.

100 Clinical Results associated with Lamivudine/Zidovudine

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100 Translational Medicine associated with Lamivudine/Zidovudine

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100 Patents (Medical) associated with Lamivudine/Zidovudine

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85

Literatures (Medical) associated with Lamivudine/Zidovudine

01 May 2018·Multiple Sclerosis and Related DisordersQ3 · MEDICINE

Could antiretrovirals be treating EBV in MS? A case report

Q3 · MEDICINE

Article

Author: Natalia C. Drosu ; Elazer R. Edelman ; David E. Housman

We present the case of an HIV-negative patient clinically diagnosed with relapsing-remitting MS who achieved significant disease improvement on Combivir (zidovudine/lamivudine). Within months of treatment, the patient reported complete resolution of previously unremitting fatigue and paresthesiae, with simultaneous improvements in lesion burden detected by MRI. All improvements have been sustained for more than three years. This response may be related to the action of zidovudine as a known inhibitor of EBV lytic DNA replication, suggesting future directions for clinical investigation.

01 Aug 2017·Mutation Research/Genetic Toxicology and Environmental MutagenesisQ3 · MEDICINE

In vivo genotoxicity evaluation of efavirenz (EFV) and tenofovir disoproxil fumarate (TDF) alone and in their clinical combinations in Drosophila melanogaster

Q3 · MEDICINE

Article

Author: de Moraes Filho, Aroldo Vieira ; Rohde, Cláudia ; Cunha, Kênya Silva ; de Jesus Silva Carvalho, Cláudia ; Verçosa, Cícero Jorge ; de Melo E Silva, Daniela ; Gonçalves, Macks Wendhell ; Chen-Chen, Lee

This study focuses on the antiretrovirals efavirenz (EFV), a non-nucleoside reverse transcriptase inhibitor, and tenofovir disoproxil fumarate (TDF), an oral prodrug of tenofovir analog of adenosine 5'-monophosphate, which belongs to the class of nucleotide reverse transcriptase inhibitors. Both compounds act on the mechanisms of HIV replication, inhibiting the action of reverse transcriptase and thus preventing viral DNA synthesis. The toxic and genotoxic potential of EFV and TDF alone and in combinations {EFV+combivir [zidovudine (AZT)+lamivudine (3TC)] and TDF+3TC} were assessed using the comet assay and the somatic mutation and recombination test (SMART) in Drosophila melanogaster. The results indicate that EFV was toxic at high concentrations and induced genotoxicity using the comet assay, but showed neither mutagenic nor recombinogenic effects using SMART. In combination with combivir, EFV exhibited antagonic genotoxic effects in both tests. Inversely, TDF did not show toxicity but induced genotoxicity at all concentrations tested in both the comet assay and SMART. The prevalence of recombinogenic events in all treatments with TDF alone and in combination with 3TC was detected using SMART. Homologous recombination is an important parameter to be taken into consideration in the evaluation of carcinogenicity of medicines used in antiretroviral therapy regimens, due to the need for lifelong adherence and the unknown effects of long-term treatments.

18 Oct 2016·Accounts of Chemical ResearchQ1 · CHEMISTRY

Discovery and Development of the Anti-Human Immunodeficiency Virus Drug, Emtricitabine (Emtriva, FTC)

Q1 · CHEMISTRY

Article

Author: Liotta, Dennis C. ; Painter, George R.

The HIV/AIDS epidemic, which was first reported on in 1981, progressed in just 10 years to a disease afflicting 10 million people worldwide including 1 million in the US. In 1987, AZT was approved for treating HIV/AIDS. Unfortunately, its clinical usefullness was severly limited by associated toxicities and the emergence of resistance. Three other drugs that were approved in the early 1990s suffered from similar liabilities. In 1990, the Liotta group at Emory University developed a highly diastereoselective synthesis of racemic 3'-thia-2',3'-dideoxycytidine and 3'-thia-2',3'-5-fluorodideoxycytidine and demonstrated that these compounds exhibited excellent anti-HIV activity with no apparent cytotoxicity. Subsequently, the enantiomers of these compounds were separated using enzyme-mediated kinetic resolutions and their (-)-enantiomers (3TC and FTC, respectively) were found to have exceptionally attractive preclinical profiles. In addition to their anti-HIV activity, 3TC and FTC potently inhibit the replication of hepatitis B virus. The development of FTC, which was being carried out by Burroughs Wellcome, had many remarkable starts and stops. For example, passage studies indicated that the compound rapidly selected for a single resistant mutant, M184V, and that this strain was 500-1000-fold less sensitive to FTC than was wild-type virus. Fortunately, it was found that combinations of AZT with either 3TC or FTC were synergistic. The effectiveness of AZT-3TC combination therapy was subsequently demonstrated in four independent clinical trials, and in 1997, the FDA approved Combivir, a fixed dose combination of AZT and 3TC. In phase 1 clinical trials, FTC was well tolerated by all subjects with no adverse events observed. However, the development of FTC was halted by the aquistition of Wellcome PLC by Glaxo PLC in January 1995. In 1996, Triangle Pharmaceuticals licensed FTC from Emory and initiated a series of phase I/II clinical studies that demonstrated the safety and efficacy of the drug. In August 1998, FTC was granted "Fast Track" status, based primarily on its potential for once daily dosing. While the outcomes of two subsequent phase III trials were positive, a third phase III clinical trial involving combinations of 3TC or FTC with stavudine and neviripine had to be terminated due to serious liver-related adverse events. Although analysis of the data suggested that the liver toxicity was due to neviripine, the FDA decided that the study could not be used for drug registration. Ultimately, in January 2003, Gilead Sciences acquired Triangle Pharmaceuticals and completed the development of FTC (emtricitabine), which was approved for once a day, oral administration in July 2003. A year later, Truvada, a once a day, oral, fixed dose combination of emtricitabine and tenofovir disoproxyl fumarate received FDA approval and quickly became the accepted first line therapy when used with a third antiretroviral agent. In July 2006, the FDA approved Atripla, a once a day, oral, fixed dose combination of emtricitabine, tenofovir disoproxyl fumarate, and efavirenz, which represented the culmination of two decades of research that had transformed AIDS from a death sentence to a manageable chronic disease.

1

News (Medical) associated with Lamivudine/Zidovudine

27 Oct 2008

·www.biospace.com

Pfizer Inc.’s Novel HIV/AIDS Treatment Selzentry(TM) (Maraviroc) Demonstrates Increased Efficacy Rate In Treatment-Naïve HIV Patients

NEW YORK--(BUSINESS WIRE)--Patients taking Selzentry, in combination with Combivir® (zidovudine/lamivudine) and selected by an enhanced sensitivity tropism test to screen patients, experienced a 68 percent rate of virologic suppression to undetectable levels, according to the MERIT ES (Reanalysis of the MERIT Study with the Enhanced Tro ) reanalysis presented at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC™)/ 46th Annual Meeting of the Infectious Diseases Society of America (IDSA) in Washington D.C., USA.

100 Deals associated with Lamivudine/Zidovudine

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
HIV Infections	NO	ViiV Healthcare BV	18 Mar 1998
HIV Infections	LI	ViiV Healthcare BV	18 Mar 1998
HIV Infections	IS	ViiV Healthcare BV	18 Mar 1998
HIV Infections	EU	ViiV Healthcare BV	18 Mar 1998

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
HIV Infections	Preclinical	US	ViiV Healthcare Co.	26 Sep 1997

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


VISEND (IAS2020)	Not Applicable	-	-	Tenofovir-disoproxil-fumarate, Lamivudine and Dolutegravir (TLD)	jqorsjiuyk(icuqjqbjuw) = eejayvmrvs qzjggtzahj (zcwvocekno, (179)) View more	-	01 Jan 2020
				Tenofovir-alafenamide, Emtricitabine and Dolutegravir (TAFED)	jqorsjiuyk(icuqjqbjuw) = domrccuqoa qzjggtzahj (zcwvocekno, (449)) View more
NCT00270296 (CTgov)	Phase 2	HIV Infections	730	Lamivudine/Zidovudine+Lopinavir/ritonavir	sajvgcpeoi(dbdqkmpytv) = zvsbwobkog bjsukfxpxa (jmyfkxbcqk, qfkbholhxp - ikaeoaghyi) View more	-	05 Jun 2017
NCT01352715 (A5273 \| SELECT, CTgov)	Phase 3	HIV Infections	515	Lopinavir/ritonavir+raltegravir (Arm A: LPV/r Plus RAL)	gymrnoyobb(gmpbyqyflw) = jvzpuhptbl lwhglrfkvz (tqndtrfucj, slajlhcxqk - kbrkhwogur) View more	-	06 Jan 2016
				Abacavir/lamivudine+Zidovudine+Abacavir+Lamivudine/zidovudine+Abacavir/lamivudine/zidovudine+Emtricitabine/tenofovir disoproxil fumarate+Lamivudine+Lopinavir/ritonavir (Arm B: LPV/r Plus Best Available NRTIs)	gymrnoyobb(gmpbyqyflw) = gordhafkni lwhglrfkvz (tqndtrfucj, utagzgnpxi - bhsnnjfitk) View more
NCT01565889 (CTgov)	Phase 1/2	HIV Infections \| Hepatitis C	52	EFV/FTC/TDF+SOF (Part A: SOF+EFV/FTC/TDF (Cohort 1))	tlpxcylezo(vtmbdtpczx) = oftspyrujs hvlnxguyqr (jpglatakgd, zmxrkjngqr - bensmcizpm) View more	-	01 Oct 2014
				SOF+ZDV/3TC+EFV (Part A: SOF+EFV+ZDV/3TC (Cohort 2))	tlpxcylezo(vtmbdtpczx) = bhzwmgoaqf hvlnxguyqr (jpglatakgd, qtofxjyepg - esogehzuag) View more
NCT00110305 (TMC278-C204, CTgov)	Phase 2	HIV Infections	368	Combivir+Truvada+TMC278 25 mg (TMC278 25 mg)	ktwanfjhvb(wvefweejki) = svzzydcxtc jdaienfgou (fsvyauxaqk, nqtywmwgoi - nkddishaan) View more	-	28 Oct 2013
				Combivir+Truvada+TMC278 75 mg (TMC278 75 mg)	ktwanfjhvb(wvefweejki) = vyzdtvncmh jdaienfgou (fsvyauxaqk, xqcjkvschu - tflffqqtus) View more
NCT00098293 (MERIT, CTgov)	Phase 3	HIV Infections	916	CBV+Maraviroc (Maraviroc Once Daily + CBV (DB), Then Twice Daily + CBV (OL))	zbtdbatexr(ltlslzinjy) = oogydmhmuc nazzkswbex (hcklvwmjng, wysevpmoav - ftvpsgifdk) View more	-	05 Oct 2012
				CBV+Maraviroc (Maraviroc Twice Daily + CBV (DB))	zbtdbatexr(ltlslzinjy) = vmawzkatuy nazzkswbex (hcklvwmjng, ldddqmysfq - dhbyjtbtgn) View more
NCT00084136 (PEARLS, CTgov)	Phase 4	HIV Infections	1,571	Lamivudine/Zidovudine+Efavirenz (ZDV/3TC+EFV)	tetgzhbmst(wfjsjaplhu) = rabvgluqcy spyoethtfu (pcdbmagzne, zqykquoszr - cfxoryleys) View more	-	09 Aug 2011
				Atazanavir+Didanosine (enteric-coated)+Emtricitabine (ddI+FTC+ATV)	tetgzhbmst(wfjsjaplhu) = ryucdvbfat spyoethtfu (pcdbmagzne, afwyzfvxwo - snvraonqmw) View more
IAS2011	Not Applicable	-	450	sd-NVP plus sd-ruvada	hqxmxffomr(azcgrlcvje) = lbhbylwyfg hcarirdosa (bewdqfkxfc )	-	01 Jan 2011
				sd-NVP and 7 days of combivir	hqxmxffomr(azcgrlcvje) = jieintggbi hcarirdosa (bewdqfkxfc )
NCT00098293 (MERIT, Pubmed \| Am J Trop Med Hyg) Manual	Phase 3	HIV Infections	721	Lamivudine/Zidovudine+Maraviroc	(wbmslszgmh) = zoqqsrmuds muasyoqsxa (tuyqjohbzt ) View more	Non-inferior	15 Mar 2010
				Lamivudine/Zidovudine+Efavirenz	(wbmslszgmh) = wlhkexrjjt muasyoqsxa (tuyqjohbzt ) View more
RECOMB trial (IAS2009)	Not Applicable	-	80	FTC/TDF (TVD) (Switching to TVD)	oflqthvacm(klrfrndnlo) = ocljijirhu cedzfxlzms (ilavieipwl ) View more	-	01 Jan 2009
				Continuing on AZT/3TC	oflqthvacm(klrfrndnlo) = dxvvlscvdf cedzfxlzms (ilavieipwl ) View more