Delving into the Latest Updates on Artesunate/Pyrimethamine/Sulfalene with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

AS/SP, Co-Arinate, Coarinate

Target

ATP2A1 x DHFR x DHPS x SERCA2

Mechanism

ATP2A1 inhibitors(Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 inhibitors), DHFR inhibitors(Dihydrofolate reductase inhibitors), DHPS inhibitors(Dihydropteroate synthase inhibitors)

Therapeutic Areas

Infectious Diseases

Active Indication

Malaria

Inactive Indication

Malaria, FalciparumSchistosomiasis Haematobia

Originator Organization

Dafra Pharma NV

Active Organization

Dafra Pharma NV

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

Login to view timeline

Structure/Sequence

Molecular FormulaC11H12N4O3S

InChIKeyKXRZBTAEDBELFD-UHFFFAOYSA-N

CAS Registry152-47-6

View All Structures (2)

The purpose of this study is to evaluate the efficacy of praziquantel versus As+SMP (Co-Arinate FDC ®) in the treatment of Schistosoma haematobium in 6-15 year old Malian children. The nul-hypothesis in this study is that the combination of As+SMP is more effective than praziquantel in the treatment of S. haematobium infected children.

Start Date01 Aug 2007

Sponsor / Collaborator

Dafra Pharma NV

NCT00484900

/ CompletedPhase 3

Open Randomized Multi-Centre Trial, Comparing Artesunate-Sulfamethoxypyrazine-Pyrimethamine FDC Over 3 Days, Artesunate-Sulfamethoxypyrazine-Pyrimethamine FDC Over 48 Hours and Artemether-Lumefantrine FDC Over 3 Days on P. Falciparum Malaria

The purpose of this open randomised multi-centre clinical trial is to test the hypothesis that three pills of the fixed dose combination artesunate/sulfamethoxypyrazine/pyrimethamine, administered over 24 hours is not inferior in efficacy to the same drug administered over 48 hours and that the fixed dose combination artesunate/sulfamethoxypyrazine/pyrimethamine As/SMP fdc, independently of the duration of its dose interval, is not inferior in efficacy to 6 - 24 pills (number of pills administered to respectively children and adults)of the 60 hours treatment of artemether/lumefantrine for the treatment of uncomplicated P. falciparum malaria.

Start Date01 May 2006

Sponsor / Collaborator

Dafra Pharma NV

NCT00127998

/ CompletedNot ApplicableIIT

Characterization of Novel Molecular Tools for the Epidemiological Surveillance of Antimalarial Drug Resistance in Mali

Resistance of Plasmodium falciparum (malaria) to current antimalarial drugs and the continuing development of resistance to new antimalarial formulations is one of the major obstacles to effective malaria control and case management. Efficient, comprehensive and validated methods for monitoring drug resistance in advance of the development of resistance to the antimalarial drugs that are in use are urgently needed. Molecular markers of genetic polymorphisms that give rise to resistant P. falciparum parasites and methods in population genetics for evaluating the data can be valuable tools for monitoring drug resistance in the field. This study aims to:
Prospectively measure the in vivo response of P. falciparum malaria in Mali to several different antimalarial drugs and drug combinations: chloroquine (CQ), sulfadoxine-pyrimethamine (SP), amodiaquine (AQ), sulfadoxine-pyrimethamine in combination with amodiaquine (SP/AQ), amodiaquine in combination with artesunate (AQ/AS), sulfadoxine-pyrimethamine in combination with artesunate (SP/AS), and artemether-lumefantrine (Co-artem). In one site with preliminary data showing a high rate of P. falciparum resistance to mefloquine (MQ), this drug will also be tested.
Measure the frequencies of molecular markers for antimalarial drug resistance, and examine how those results relate to the efficacy of these drugs in treating clinical malaria
Measure drug levels at 3 days and correlate with efficacy results.
Examine early clinical, parasitologic, and clinical predictors of late treatment failure.
Use the knowledge gained in Aims 1-3 to develop a molecular tool for a countrywide resistance surveillance system for antimalarial drugs.

Start Date01 Jul 2005

Sponsor / Collaborator

Centers for Disease Control & Prevention

100 Clinical Results associated with Artesunate/Pyrimethamine/Sulfalene

Login to view more data

100 Translational Medicine associated with Artesunate/Pyrimethamine/Sulfalene

Login to view more data

100 Patents (Medical) associated with Artesunate/Pyrimethamine/Sulfalene

Login to view more data

30

Literatures (Medical) associated with Artesunate/Pyrimethamine/Sulfalene

01 Jul 2019·Journal of helminthology

Efficacy of artemisinin–naphthoquine phosphate against Schistosoma haematobium adult flukes: dose–effect relationship and tegumental alterations

Article

Author: Taman, A ; El-Beshbishi, S N ; Ayoub, M ; El Bardicy, S ; Tadros, M

Abstract:

Schistosoma haematobium and Schistosoma mansoni infections have broadly overlapping geographical distributions. Praziquantel is the only treatment for human schistosomiasis, so drug tolerance and/or resistance are major concerns. Artemisinin–naphthoquine phosphate (CO-ArNp), an artemisinin-based combination therapy endorsed by the World Health Organization as a gold standard therapy for malaria, has also been identified as a promising treatment for S. mansoni. In this in vitro study, we tested the effect of 1–40 μg/ml CO-ArNp on S. haematobium worms, and inspected tegumental changes by using scanning electron microscopy (SEM), aiming to determine if this combination therapy has a broad-spectrum antischistosomal activity. Incubation of S. haematobium adults with 20 or 30 μg/ml CO-ArNp caused 100% mortality of worms within 72 or 48 h, respectively. SEM examination showed extensive tegumental alterations such as oedema, constriction, shortening and loss of spines, fissuring, sloughing and perforation, resulting in exposure of the underlying basal lamina, mainly in treated male schistosomes. Besides the well-established potent efficacy, bioavailability, tolerability and safety of the antimalarial artemisinin–naphthoquine phosphate combined therapy, these results may also suggest its possible utilization as a new broad-spectrum antischistosomal agent.

01 Jun 2019·Transactions of the Royal Society of Tropical Medicine and HygieneQ4 · MEDICINE

Biological activity of artemisinin-naphthoquine phosphate on Schistosoma haematobium stages and the vector Bulinus truncatus

Q4 · MEDICINE

Article

Author: El-Beshbishi, Samar N ; El Bardicy, Samia ; Taman, Amira ; Ayoub, Magda ; Tadros, Menerva

BACKGROUND:

Schistosoma haematobium infection is a major public health problem in most of Africa and the Middle East and praziquantel remains the only drug used for schistosomiasis control, therefore emergence of drug resistance is unavoidable. The antimalarial artemisinin-naphthoquine phosphate combination (co-ArNp) was recently documented to have promising effects on Schistosoma mansoni and its snail host.

METHODS:

We conducted this in vitro study to assess the bioactivity of co-ArNp on S. haematobium and its snail vector Bulinus truncatus.

RESULTS:

Treatment of S. haematobium worms with 1 μg/ml co-ArNp for 24 h reduced worm motility, while 20 μg/ml resulted in 25-100% mortality of adult flukes within 48-72 h. Incubation of S. haematobium miracidia and cercariae with the molluscicidal co-ArNp (50% lethal concentration 7.5 μg/ml) killed all the free larval stages within 40 and 15 min, respectively. Also, exposure of B. truncatus adult snails to 20 ppm of the combined regimen caused a mortality rate of 100% within 24 h.

CONCLUSIONS:

Co-ArNp therapy has also shown encouraging activity against the other major human schistosome, S. haematobium, as well as its vector.

01 Sep 2018·Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseasesQ3 · MEDICINE

Spatio-temporal distribution of PfMDR1 polymorphism among uncomplicated Plasmodium falciparum malaria cases along international border of north east India

Q3 · MEDICINE

Article

Author: Valecha, Neena ; Yadav, Chander Prakash ; Goomber, Shelly ; Anvikar, Anup ; Mishra, Neelima

PfMDR1 single nucleotide polymorphisms (SNP) are good correlate markers for antimalarial drug resistance worldwide. Present study is a comprehensive view of screening of PfMDR1 polymorphism to antimalarials practiced with geography and time. Study sites Mizoram, Tripura, Meghalaya chosen are at multivariate drug pressure due to cross border migration and transmission. Mizoram is gateway to south east Asia through Myanmar whereas Tripura, Meghalaya share porous border with Bangladesh. Baseline finger pricked blood stained filter paper for confirmed uncomplicated Plasmodium falciparum infected patients (year 2015) were obtained from National Institute of Malaria Research, New Delhi, India. PfMDR1 polymorphism for codon N86Y, Y184F, D1246Y was determined by PCR-RFLP, further confirmed by sequencing. There observed marked predominance of Plasmodium isolates with PfMDR1 wild type alleles for all codons under study i.e. 86, 184, 1246. Spatially, Plasmodium isolates from Mizoram were most diverse with co-existence of PfMDR1 genotype with NYD, YYD, NFD haplotypes, followed by Tripura. Isolates from Meghalaya were of all NYD haplotype. Reports, referring to screening of PfMDR1 SNPs to CQ/SP/AS-SP across India, were archived. Temporal study show distinct rise in proportion of PfMDR1 wild type N86 allele since introduction of Artemether-Lumefantrine as first line antimalarial. Hence spatio-temporal screening of Plasmodium population with PfMDR1 single nucleotide polymorphism accounts for its association with antimalarial susceptibility and validate PfMDR1 SNPs as antimalarial drug resistant marker.

100 Deals associated with Artesunate/Pyrimethamine/Sulfalene

Login to view more data

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	P01B	-

R&D Status

Approved

10 top approved records.

Login

to view more data

Indication	Country/Location	Organization	Date
Malaria	-	Dafra Pharma NV	-

Developing

10 top R&D records.

Login

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Schistosomiasis Haematobia	Phase 3	ML	Dafra Pharma NV	01 Aug 2007
Malaria, Falciparum	Phase 3	CM	Dafra Pharma NV	01 May 2006
Malaria, Falciparum	Phase 3	ML	Dafra Pharma NV	01 May 2006
Malaria, Falciparum	Phase 3	RW	Dafra Pharma NV	01 May 2006
Malaria, Falciparum	Phase 3	SD	Dafra Pharma NV	01 May 2006