amodiaquine hydrochloride / Generic mfg. - LARVOL DELTA

Plasmodium falciparum isolates: ex vivo drug response. (PubMed, J Antimicrob Chemother) - "Clinical isolates from coastal Ghana remain susceptible to artemisinin derivatives in commonly used ACTs in Ghana. However, we observed lower susceptibility to the ACT partner drugs lumefantrine and amodiaquine, suggesting the emergence of drug-tolerance phenotypes. Consistent surveillance of drug phenotype-genotype is needed to support ACT efficacy in Ghana."

Journal • Preclinical • Infectious Disease • Malaria • ABCB1

A well-characterized mechanistic Model for exploring known or hypothesized T cell -mediated drug induced liver injury: current capabilities and challenges for future predictivity. (PubMed, Expert Opin Drug Metab Toxicol) - "To overcome deficits in quantitative data characterizing CD8+ T cell-mediated DILI, a translational strategy leveraged a well-defined mouse ovalbumin (OVA) antigen model and adapted it to represent mouse amodiaquine (AQ)-specific CD8+ T cell-mediated DILI, with further adaptations to represent human AQ-specific CD8+ T cell-mediated DILI...The DILIsym CD8+ T cell sub-model is well-positioned for systematic testing to improve our understanding of CD8+ T cell-mediated DILI. It is not yet predictive but indicates a promising direction to reduce DILI events in drug development."

Journal • Hepatology • Liver Failure • CD8

Molecular Docking, Toxicity Study and In Vitro Antimalarial Evaluation of Pyrazole Substituted 1,3,5-Triazine Derivatives. (PubMed, Exp Parasitol) - "The development of resistance to antimalarial drugs such as chloroquine, amodiaquine, artemisinin, and antifolates is a major health concern, prompting more research into new antimalarial therapies. Compounds 7j and 7i exhibited considerable antimalarial efficacy against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains of P. falciparum, with IC50 values ranging from 23.78 to 83.36 μM and 30.89 to 64.24 μM, respectively. These pyrazole-substituted 1,3,5-triazine derivatives could be utilized to find a novel class of Pf-DHFR-TS inhibitors."

Journal • Preclinical • Infectious Disease • DHFR

Design, Synthesis, and Anti-SARS-CoV-2 Activity of Amodiaquine Analogs. (PubMed, Chem Pharm Bull (Tokyo)) - "In this study, we designed and synthesized new anti-SARS-CoV-2 drugs based on the chemical structure of amodiaquine, which is known as an antimalarial drug. Consequently, we have identified amodiaquine analogs functionalized with dialkylamino-pendant aminophenol moieties that possess a high level of anti-SARS-CoV-2 activity with a low level of toxicity."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Ab-initio Molecular Dynamics and Density Functional Theory Study of Amodiaquine Analogues as Potential Inhibitors of β-haematin Crystallization. (PubMed, Curr Med Chem) - "The findings from this study are valuable because they can aid the design and understanding of new therapeutic molecules that could be used to treat drug-resistant malaria, a global threat of today."

Journal • Infectious Disease • Malaria

Evaluation of seasonal malaria chemoprevention implementation in the Upper East region of Northern Ghana. (PubMed, Malar J) - "Despite achieving an average coverage of 87% per cycle, it falls short of the national target of 90%. Notable reasons for drop-outs and non-adherence were, the caregiver being unavailable during the distribution, highlighting the need for diversified approaches in SMC campaigns to enhance coverage, and adherence, and maximize intervention benefits."

Journal • Infectious Disease • Malaria

Impact of variation in CYP3A and CYP2C8 on tucatinib metabolic clearance in human liver microsomes. (PubMed, Drug Metab Dispos) - "CYP2C8 and CYP3A activities were quantitated by liquid chromatography-tandem mass spectrometry analysis using the following marker reactions: amodiaquine N-deethylation and midazolam 1'-hydroxylation, respectively. By elucidating how variability in CYP2C8 and CYP3A phenotypes influence tucatinib pharmacokinetics, this study has the potential to provide the framework for future studies that could inform dosing to minimize adverse events and improve therapeutic outcomes. Ultimately, understanding how individual cytochrome P450 phenotypes influence the clearance of cancer therapeutics will aid in the development of tailored regimens for diverse patient populations."

Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CYP3A4 • CYP3A5 • HER-2

THE ROLE OF STRIATAL NURR1 IN THE SOCIAL BEHAVIOR OF PRENATALLY VALPROIC ACID -EXPOSED AUTISM SPECTRUM DISORDERS MODEL MICE (ADPD 2025) - "In addition, treatment with amodiaquine, which is a kn own ligand for Nurr1, mimicked the social deficits and synaptic abnormalities in saline -exposed mice as observed in prenatally VPA-exposed mice. Taken together, our results suggest that the increase in Nurr1 expression in the striatum is a mechanism related to the changes in synaptic deficits and behavioral phenotypes of the VPA -induced ASD mouse model."

Preclinical • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Psychiatry • NR4A2

High incidence of clinical malaria among asymptomatic Plasmodium falciparum infected children receiving SMC with sulfadoxine-pyrimethamine and amodiaquine (SP + AQ) in Koulikoro, Mali. (PubMed, Malar J) - "These findings demonstrate an elevated risk of clinical malaria in asymptomatic infected children during SMC implementation. Screening and treating P. falciparum infections prior to SMC administration could substantially enhance the effectiveness of this strategy in reducing malaria morbidity in endemic areas."

Journal • Infectious Disease • Malaria

Structural and Functional Implications of MIT2 and NT2 Mutations in Amodiaquine and Piperaquine Resistant Plasmodium berghei Parasites. (PubMed, Exp Parasitol) - "These findings suggest that selection pressure from AQ and PQ leads to mutations in MIT2 and NT2. Further investigation is required to understand how these mutations affect drug susceptibility on a functional level."

Journal • Infectious Disease • Malaria • ABCG2

Phase one of a hybrid effectiveness-implementation study to assess the feasibility, acceptability and effectiveness of implementing seasonal malaria chemoprevention in Nampula Province, Mozambique. (PubMed, Malar J) - "Results suggest that SMC was effective at preventing clinical malaria, did not significantly impact resistance profile, and was feasible and acceptable in the context. Phase two will assess SMC impact in reducing malaria incidence and if chemoprevention efficacy of SPAQ is impacted by drug resistance and drug concentrations."

Journal • Infectious Disease • Malaria

Dose-Optimization of a Novel Co-Formulated Triple Combination Antimalarial Therapy: Artemether-Lumefantrine-Amodiaquine. (PubMed, Clin Pharmacol Ther) - "Based on simulated total exposure and peak concentrations, an optimal dose regimen was developed resulting in an extension of the current 4 weight bands to a total of 5 weight bands to generate equivalent exposures in all body weight groups and minimize the fluctuation in exposure between patients. The proposed drug-to-drug ratio of artemether-lumefantrine-amodiaquine (20:120:40 mg) was kept constant throughout the dosing bands in order to simplify manufacturing, implementation, and further development of a fixed-dose co-formulated product."

Journal • Infectious Disease • Malaria • Pediatrics

Prevalence of Plasmodium falciparum drug resistance markers pfcrt K76T and pfaat1 S258L in southern Rwanda, 2010 to 2023. (PubMed, J Infect Dis) - "The persistence of pfcrt K76T 20 years after abolishing chloroquine indicates ongoing drug selection or importation. The fixation of pfaat1 S258L argues against a major fitness cost of this variant in Huye. Partial artemisinin resistance increases in Rwanda, and molecular markers indicate compromised lumefantrine efficacy. The observed pfcrt and pfaat1 signatures in the study area might guide artemisinin partner drug alternatives."

Journal • Infectious Disease • Malaria

PBPK-Led Assessment of Antimalarial Drug Concentrations in Breastmilk: A Strategy for Optimal Use of Prediction Methods to Guide Decision Making in an Understudied Population. (PubMed, CPT Pharmacometrics Syst Pharmacol) - "Physiologically based pharmacokinetic (PBPK) modeling was used to predict milk-to-plasma (M/P) ratios, infant daily doses (IDD) and relative infant doses (RID) for five antimalarials with clinical lactation data (chloroquine, pyrimethamine, piperaquine, mefloquine and primaquine)...RID was  10% for lumefantrine and tafenoquine. For atovaquone, RID was > 10% with Model 1 but not Model 2...These prediction methodologies can be used, alongside any licensed dosing information for < 1 year-olds, to evaluate whether a clinical lactation study is necessary and to inform drug label or policy recommendations. The ultimate goal is to better inform optimal treatment for lactating women supporting malaria eradication."

Journal • Infectious Disease • Malaria

Worldwide study of the taste of bitter medicines and their modifiers. (PubMed, Chem Senses) - "The taste solutions were five medicines, tenofovir alafenamide (TAF), moxifloxacin, praziquantel, amodiaquine, and propylthiouracil (PROP), and four other solutions, TAF mixed with sucralose (sweet, reduces bitterness) or 6-methylflavone (tasteless, reduces bitterness), sucralose alone, and sodium chloride alone. Genetic analysis showed that people with variants in one bitter receptor variant gene (TAS2R38) reported PROP was more bitter than did those with a different variant (p= 7.6e-19) and that people with either an RIMS2 or a THSD4 genotype found sucralose more bitter than did others (p=2.6e-8, p=7.9e-11, resp.). Our findings may help guide the formulation of bad-tasting medicines to meet the needs of those most sensitive to them."

Journal • THSD4

Low-Cost and Portable Biosensor Based on Monitoring Impedance Changes in Aptamer-Functionalized Nanoporous Anodized Aluminum Oxide Membrane. (PubMed, Micromachines (Basel)) - "The specificity of the sensor response is characterized by exposure to varying concentrations of chloroquine, which is similar in structure to amodiaquine but does not bind to the OR7 aptamer. The sensing response measured using both the portable impedance reader and the commercial potentiostat showed a similar dynamic response and detection threshold. The specific and sensitive sensing results for amodiaquine demonstrate the efficacy of the low-cost and portable biosensor."

Journal • Infectious Disease • Malaria

Assessing the Acceptability and Feasibility of Five Cycles of Seasonal Malaria Chemoprevention in Côte d'Ivoire. (PubMed, Trop Med Infect Dis) - "Seasonal malaria chemoprevention with sulfadoxine-pyrimethamine + amodiaquine (SP + AQ) was administered monthly to eligible children over five months. A qualitative approach and quantitative surveys were used to assess the strategy acceptability and feasibility in the study area. Overall, there was a positive perception, attitude, and adherence towards the seasonal malaria chemoprevention in this study area."

Journal • Infectious Disease • Malaria

Prevalence, characteristics, and treatment outcome of congenital malaria in Nigeria: a systematic review. (PubMed, Malar J) - "The findings highlight the need for improved diagnostic tools, standardized treatment protocols, and targeted interventions in high-burden areas. Further research is required to investigate the long-term health outcomes of neonates with congenital malaria and to evaluate the effectiveness of different treatment strategies. By addressing these gaps, effective prevention and management strategies can be developed to reduce the burden of congenital malaria in Nigeria."

Journal • Review • Infectious Disease • Malaria

SMC-RST: Boosting the Impact of SMC Through Simultaneous Screening and Treatment of Roommates (clinicaltrials.gov) - P4 | N=526 | Completed | Sponsor: Institut de Recherche en Sciences de la Sante, Burkina Faso | Not yet recruiting ➔ Completed | N=789 ➔ 526

Enrollment change • Trial completion • Infectious Disease • Malaria

Effectiveness of sulfadoxine-pyrimethamine plus amodiaquine and dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in Uganda: a three-arm, open-label, non-inferiority and superiority, cluster-randomised, controlled trial. (PubMed, Lancet Infect Dis) - P4 | "SPAQ and dihydroartemisinin-piperaquine effectively reduced malaria in children younger than 5 years, with no safety concerns. There was no evidence of resistance selection by SMC. Although these findings support SPAQ-based SMC in Eastern and Southern Africa, ongoing resistance surveillance and efficacy monitoring are essential for sustained impact."

Head-to-Head • Journal • Infectious Disease • Malaria • ABCB1 • ABCC1 • DHFR

Impact of seasonal malaria chemoprevention timing on clinical malaria incidence dynamics in the Kedougou region, Senegal. (PubMed, PLOS Glob Public Health) - "Seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine is recommended by the World Health Organization since 2012 for clinical malaria prevention in children in the Sahelian region of Africa. While protecting children under 10 years, SMC warrants adjustment to reduce exposure before the next round, to increase protection of 5-9 years, and to cover the high transmission period completely. The addition of a 5th round of SMC in 2023 was necessary to cover the end of the transmission season, but individual-level studies are required to ensure that drug efficacy and adequate dosing are maintained."

Journal • Infectious Disease • Malaria

Caregiver acceptability of seasonal malaria chemoprevention in two districts in the Upper West region, Ghana: a cross-sectional study. (PubMed, Malar J) - "Health authorities and stakeholders can work towards bridging the gap between knowledge and SMC treatment practices of caregivers through continuous education, adherence counseling, and effective monitoring of SMC practices in malaria-endemic countries."

Journal • Observational data • Infectious Disease • Malaria

Effect of mass drug administration on malaria incidence in southeast Senegal during 2020-22: a two-arm, open-label, cluster-randomised controlled trial. (PubMed, Lancet Infect Dis) - P=N/A | "In southeast Senegal, a low-to-moderate transmission setting where malaria-control measures have been scaled up, three cycles of MDA with dihydroartemisinin-piperaquine plus single, low-dose primaquine was safe and reduced malaria burden during the intervention year. However, its sustained effect was weak and continuation of MDA or another transmission-reducing strategy could be required."

Journal • Infectious Disease • Malaria

Amodiaquine Analogs Are Potent Inhibitors of Interleukin-6 Production Induced by Activation of Toll-Like Receptors Recognizing Pathogen Nucleic Acids. (PubMed, Biol Pharm Bull) - "In J774.1 murine macrophages, ADQ inhibited interleukin-6 (IL-6) production induced by TLR3 agonist poly(I:C), TLR7 agonist imiquimod, and TLR9 agonist cytosine-phosphate-guanosine oligodeoxynucleotide (CpG ODN) with IC50 values of 2.43, 3.48, and 0.0359 µM, respectively, indicating that ADQ has a high inhibitory selectivity for TLR9 signaling. ADQ and its analogs appear to inhibit the activity of TLRs recognizing pathogen nucleic acids via alkalinization of endolysosomes. Our results suggest that ADQ analogs are promising candidates as therapeutic agents for cytokine storms mediated by TLRs recognizing pathogen nucleic acid with reduced side effects."

Journal • Infectious Disease • Inflammation • Novel Coronavirus Disease • Respiratory Diseases • IL6 • TLR8

Asymptomatic Plasmodium falciparum infections and determinants of carriage in a seasonal malaria chemoprevention setting in Northern Cameroon and south Senegal (Kedougou). (PubMed, Malar J) - "Under five years asymptomatic Plasmodium infection in northern Cameroon prior to SMC season remained high in 2018, irrespective of history of SMC implementation in the study areas in Cameroon. Compared to Adamaoua, peak asymptomatic malaria parasite rate was observed in children 5-10 years, which is out of the SMC target age-range. Health area, last infection within the past month and to a lesser extent gender affected the association between age and asymptomatic carriage in all sites except the North region of Cameroon, indicating wide heterogeneity in risk of malaria among the general population in that geography. Follow-up studies designed to measure SMC effects in Cameroon are warranted as it may become necessary to extend age of SMC eligibility to 10 years, as is practiced in Senegal."

Journal • Infectious Disease • Malaria