Palang Chotsiri

Mahidol Oxford Tropical Medicine Research Unit

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Joel Tärning

Mahidol Oxford Tropical Medicine Research Unit

Richard M. Hoglund

University of Oxford

Nicholas J. White

University of Oxford

Thanaporn Wattanakul

Mahidol University

Warunee Hanpithakpong

Mahidol Oxford Tropical Medicine Research Unit

Ivan Scandale

Drugs for Neglected Diseases Initiative

Nicholas Day

Mahidol University

François Nosten

Shoklo Malaria Research Unit

Paul-Rémi Petit

Aix-Marseille Université

Joseph F. Standing

University College London

Cooperative Institutions

Mahidol University

Mahidol Oxford Tropical Medicine Research Unit

University of Oxford

Inserm

Angkor Hospital for Children

Institut de Recherche pour le Développement

London School of Hygiene & Tropical Medicine

Kenya Medical Research Institute

Aix-Marseille Université

Hospital for Tropical Diseases

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Population pharmacokinetics and electrocardiographic effects of dihydroartemisinin–piperaquine in healthy volunteers

British Journal of Clinical Pharmacology (2017)

Palang Chotsiri Thanaporn Wattanakul Richard M. Hoglund Borimas Hanboonkunupakarn Sasithon Pukrittayakamee

The aims of the present study were to evaluate the pharmacokinetic properties of dihydroartemisinin (DHA) and piperaquine, potential drug-drug interactions with concomitant primaquine treatment, and piperaquine effects on the electrocardiogram in healthy volunteers.The population pharmacokinetic properties of DHA and piperaquine were assessed in 16 healthy Thai adults using an open-label, randomized, crossover study. Drug concentration-time data and electrocardiographic measurements were evaluated with nonlinear mixed-effects modelling.The developed models described DHA and piperaquine population pharmacokinetics accurately. Concomitant treatment with primaquine did not affect the pharmacokinetic properties of DHA or piperaquine. A linear pharmacokinetic-pharmacodynamic model described satisfactorily the relationship between the individually corrected QT intervals and piperaquine concentrations; the population mean QT interval increased by 4.17 ms per 100 ng ml-1 increase in piperaquine plasma concentration. Simulations from the final model showed that monthly and bimonthly mass drug administration in healthy subjects would result in median maximum QT interval prolongations of 18.9 ms and 16.8 ms, respectively, and would be very unlikely to result in prolongation of more than 50 ms. A single low dose of primaquine can be added safely to the existing DHA-piperaquine treatment in areas of multiresistant Plasmodium falciparum malaria.Pharmacokinetic-pharmacodynamic modelling and simulation in healthy adult volunteers suggested that therapeutic doses of DHA-piperaquine in the prevention or treatment of P. falciparum malaria are unlikely to be associated with dangerous QT prolongation.

Piperaquine

Dihydroartemisinin

Population Pharmacokinetics

10.1111/bcp.13372

Cite

Citations (28)

Prevalence of physical activity counseling in primary care: A systematic review and meta-analysis

Health Promotion Perspectives (2023)

Apichai Wattanapisit Sarawut Lapmanee Sirawee Chaovalit Charupa Lektip Palang Chotsiri

Background: This systematic review aimed to summarize and evaluate the prevalence of physical activity (PA) counseling in primary care. Methods: Five databases (CINAHL Complete, Embase, Medline, PsycInfo, and Web of Science) were searched. Primary epidemiological studies on PA counseling in primary care were included. The Joanna Briggs Institute critical appraisal checklist for studies reporting prevalence data was used to assess the quality of studies. The review protocol was registered with PROSPERO (CRD42021284570). Results: After duplicate removal, 4990 articles were screened, and 120 full-text articles were then assessed. Forty studies were included, with quality assessment scores ranging from 5/9 to 9/9. The pooled prevalence of PA counseling based on 35 studies (199830 participants) was 37.9% (95% CI 31.2 to 44.6). The subgroup analyses showed that the prevalence of PA counseling was 33.1% (95% CI: 22.6 to 43.7) in females (10 studies), 32.1% (95% CI: 22.6 to 41.7) in males (10 studies), 65.5% (95% CI: 5.70 to 74.1) in people with diabetes mellitus (6 studies), 41.6% (95% CI: 34.9 to 48.3) in people with hypertension (5 studies), and 56.8% (95% CI: 31.7 to 82.0) in people with overweight or obesity (5 studies). All meta-analyses showed high levels of heterogeneity (I2=93% to 100%). Conclusion: The overall prevalence of PA counseling in primary care was low. The high levels of heterogeneity suggest variability in the perspectives and practices of PA counseling in primary care. PA counseling should be standardized to ensure its optimum effectiveness in primary care.

CINAHL

PsycINFO

10.34172/hpp.2023.31

Cite

Citations (4)

Piperaquine Pharmacokinetics during Intermittent Preventive Treatment for Malaria in Pregnancy

Antimicrobial Agents and Chemotherapy (2020)

Palang Chotsiri Julie Gutman Rukhsana Ahmed Jeanne Rini Poespoprodjo Din Syafruddin

Dihydroartemisinin-piperaquine (DP) is a long-acting artemisinin combination treatment that provides effective chemoprevention and has been proposed as an alternative antimalarial drug for intermittent preventive therapy in pregnancy (IPTp). Several pharmacokinetic studies have shown that dose adjustment may not be needed for the treatment of malaria in pregnancy with DP. However, there are limited data on the optimal dosing for IPTp. This study aimed to evaluate the population pharmacokinetics of piperaquine given as IPTp in pregnant women. Pregnant women were enrolled in clinical trials conducted in Kenya and Indonesia and treated with standard 3-day courses of DP, administered in 4- to 8-week intervals from the second trimester until delivery. Pharmacokinetic blood samples were collected for piperaquine drug measurements before each treatment round, at the time of breakthrough symptomatic malaria, and at delivery. Piperaquine population pharmacokinetic properties were investigated using nonlinear mixed-effects modeling with a prior approach. In total, data from 366 Kenyan and 101 Indonesian women were analyzed. The pharmacokinetic properties of piperaquine were adequately described using a flexible transit absorption (n = 5) followed by a three-compartment disposition model. Gestational age did not affect the pharmacokinetic parameters of piperaquine. After three rounds of monthly IPTp, 9.45% (95% confidence interval [CI], 1.8 to 26.5%) of pregnant women had trough piperaquine concentrations below the suggested target concentration (10.3 ng/ml). Translational simulations suggest that providing the full treatment course of DP at monthly intervals provides sufficient protection to prevent malaria infection. Monthly administration of DP has the potential to offer optimal prevention of malaria during pregnancy. (This study has been registered at ClinicalTrials.gov under identifier NCT01669941 and in the ISRCTN under number ISRCTN34010937.).

Piperaquine

Dihydroartemisinin

10.1128/aac.01150-20

Cite

Citations (13)

Need for a Standardized Translational Drug Development Platform: Lessons Learned from the Repurposing of Drugs for COVID-19

Microorganisms (2022)

Frauke Assmus Jean‐Sélim Driouich Rana Abdelnabi Laura Vangeel Franck Touret

In the absence of drugs to treat or prevent COVID-19, drug repurposing can be a valuable strategy. Despite a substantial number of clinical trials, drug repurposing did not deliver on its promise. While success was observed with some repurposed drugs (e.g., remdesivir, dexamethasone, tocilizumab, baricitinib), others failed to show clinical efficacy. One reason is the lack of clear translational processes based on adequate preclinical profiling before clinical evaluation. Combined with limitations of existing in vitro and in vivo models, there is a need for a systematic approach to urgent antiviral drug development in the context of a global pandemic. We implemented a methodology to test repurposed and experimental drugs to generate robust preclinical evidence for further clinical development. This translational drug development platform comprises in vitro, ex vivo, and in vivo models of SARS-CoV-2, along with pharmacokinetic modeling and simulation approaches to evaluate exposure levels in plasma and target organs. Here, we provide examples of identified repurposed antiviral drugs tested within our multidisciplinary collaboration to highlight lessons learned in urgent antiviral drug development during the COVID-19 pandemic. Our data confirm the importance of assessing in vitro and in vivo potency in multiple assays to boost the translatability of pre-clinical data. The value of pharmacokinetic modeling and simulations for compound prioritization is also discussed. We advocate the need for a standardized translational drug development platform for mild-to-moderate COVID-19 to generate preclinical evidence in support of clinical trials. We propose clear prerequisites for progression of drug candidates for repurposing into clinical trials. Further research is needed to gain a deeper understanding of the scope and limitations of the presented translational drug development platform.

Drug repositioning

Repurposing

Drug Development

Tocilizumab

Translational Research

Approved drug

10.3390/microorganisms10081639

Cite

Citations (6)

A pharmacometric approach to evaluate drugs for potential repurposing as COVID-19 therapeutics

Expert Review of Clinical Pharmacology (2022)

Thanaporn Wattanakul Palang Chotsiri Ivan Scandale Richard M. Hoglund Joel Tärning

Developing and evaluating novel compounds for treatment or prophylaxis of emerging infectious diseases is costly and time-consuming. Repurposing of already available marketed compounds is an appealing option as they already have an established safety profile. This approach could substantially reduce cost and time required to make effective treatments available to fight the COVID-19 pandemic. However, this approach is challenging since many drug candidates show efficacy in in vitro experiments, but fail to deliver effect when evaluated in clinical trials. Better approaches to evaluate in vitro data are needed, in order to prioritize drugs for repurposing.This article evaluates potential drugs that might be of interest for repurposing in the treatment of patients with COVID-19 disease. A pharmacometric simulation-based approach was developed to evaluate in vitro activity data in combination with expected clinical drug exposure, in order to evaluate the likelihood of achieving effective concentrations in patients.The presented pharmacometric approach bridges in vitro activity data to clinically expected drug exposures, and could therefore be a useful compliment to other methods in order to prioritize repurposed drugs for evaluation in prospective randomized controlled clinical trials.

Repurposing

Drug repositioning

Drug Development

10.1080/17512433.2022.2113388

Cite

Citations (5)

Mechanistic Modeling of Primaquine Pharmacokinetics, Gametocytocidal Activity, and Mosquito Infectivity

Clinical Pharmacology & Therapeutics (2021)

Palang Chotsiri Almahamoudou Mahamar Richard M. Hoglund Fanta Koïta Koualy Sanogo

Clinical studies have shown that adding a single 0.25 mg base/kg dose of primaquine to standard antimalarial regimens rapidly sterilizes Plasmodium falciparum gametocytes. However, the mechanism of action and overall impact on malaria transmission is still unknown. Using data from 81 adult Malians with P. falciparum gametocytemia who received the standard dihydroartemisinin-piperaquine treatment course and were randomized to receive either a single dose of primaquine between 0.0625 and 0.5 mg base/kg or placebo, we characterized the pharmacokinetic-pharmacodynamic relationships for transmission blocking activity. Both gametocyte clearance and mosquito infectivity were assessed. A mechanistically linked pharmacokinetic-pharmacodynamic model adequately described primaquine and carboxy-primaquine pharmacokinetics, gametocyte dynamics, and mosquito infectivity at different clinical doses of primaquine. Primaquine showed a dose-dependent gametocytocidal effect that precedes clearance. A single low dose of primaquine (0.25 mg/kg) rapidly prevented P. falciparum transmissibility.

Primaquine

Pharmacodynamics

Piperaquine

Infectivity

Dihydroartemisinin

10.1002/cpt.2512

Cite

Citations (8)

Pre-clinical evaluation of antiviral activity of nitazoxanide against SARS-CoV-2

EBioMedicine (2022)

Jean‐Sélim Driouich Maxime Cochin Franck Touret Paul-Rémi Petit Magali Gilles

To address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy.In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against SARS-CoV-2.First, we confirmed the in vitro efficacy of nitazoxanide and tizoxanide (its active metabolite) against SARS-CoV-2. Then, we demonstrated nitazoxanide activity in a reconstructed bronchial human airway epithelium model. In a SARS-CoV-2 virus challenge model in hamsters, oral and intranasal treatment with nitazoxanide failed to impair viral replication in commonly affected organs. We hypothesized that this could be due to insufficient diffusion of the drug into organs of interest. Indeed, our pharmacokinetic study confirmed that concentrations of tizoxanide in organs of interest were always below the in vitro EC50.These preclinical results suggest, if directly applicable to humans, that the standard formulation and dosage of nitazoxanide is not effective in providing antiviral therapy for Covid-19.This work was supported by the Fondation de France "call FLASH COVID-19", project TAMAC, by "Institut national de la santé et de la recherche médicale" through the REACTing (REsearch and ACTion targeting emerging infectious diseases), by REACTING/ANRS MIE under the agreement No. 21180 ('Activité des molécules antivirales dans le modèle hamster'), by European Virus Archive Global (EVA 213 GLOBAL) funded by the European Union's Horizon 2020 research and innovation program under grant agreement No. 871029 and DNDi under support by the Wellcome Trust Grant ref: 222489/Z/21/Z through the COVID-19 Therapeutics Accelerator".

Nitazoxanide

Antiviral drug

Mesocricetus

10.1016/j.ebiom.2022.104148

Cite

Citations (14)

Primaquine for uncomplicated Plasmodium vivax malaria in children younger than 15 years: a systematic review and individual patient data meta-analysis

The Lancet Child & Adolescent Health (2024)

Robert J. Commons Megha Rajasekhar Elizabeth Allen Daniel Yilma Palang Chotsiri

Primaquine, the only widely available treatment to prevent relapsing Plasmodium vivax malaria, is produced as 15 mg tablets, and new paediatric formulations are being developed. To inform the optimal primaquine dosing regimen for children, we aimed to determine the efficacy and safety of different primaquine dose strategies in children younger than 15 years.

Primaquine

10.1016/s2352-4642(24)00210-4

Cite

Citations (0)

Severe Acute Malnutrition Results in Lower Lumefantrine Exposure in Children Treated With Artemether‐Lumefantrine for Uncomplicated Malaria

Clinical Pharmacology & Therapeutics (2019)

Palang Chotsiri Lise Denoeud‐Ndam Elisabeth Baudin Ousmane Guindo Halimatou Diawara

Severe acute malnutrition ( SAM ) has been reported to be associated with increased malaria morbidity in Sub‐Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic (PK)‐pharmacodynamic study included 131 SAM and 266 non‐ SAM children administered artemether‐lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit‐absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the PK model. Mid‐upper arm circumference was associated with decreased absorption of lumefantrine (25.4% decreased absorption per 1 cm reduction). Risk of recurrent malaria episodes (i.e., reinfection) were characterized by an interval‐censored time‐to‐event model with a sigmoid maximum‐effect model describing the effect of lumefantrine. SAM children were at risk of underexposure to lumefantrine and an increased risk of malaria reinfection compared with well‐nourished children. Research on optimized regimens should be considered for malaria treatment in malnourished children.

Artemether/lumefantrine

Lumefantrine

Artemether

Severe Acute Malnutrition

10.1002/cpt.1531

Cite

Citations (35)

Pre-clinical evaluation of antiviral activity of nitazoxanide against Sars-CoV-2

bioRxiv (Cold Spring Harbor Laboratory) (2021)

Jean‐Sélim Driouich Maxime Cochin Franck Touret Paul-Rémi Petit Magali Gilles

Abstract To address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy. In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against SARS-CoV-2. First, we confirmed the in vitro efficacy of nitazoxanide and tizoxanide (its active metabolite) against SARS-CoV-2. Then, we demonstrated nitazoxanide activity in a reconstructed bronchial human airway epithelium model. In a SARS-CoV-2 virus challenge model in hamsters, oral and intranasal treatment with nitazoxanide failed to impair viral replication in commonly affected organs. We hypothesized that this could be due to insufficient diffusion of the drug into organs of interest. Indeed, our pharmacokinetic study confirmed that concentrations of tizoxanide in organs of interest were always below the in vitro EC 50 . These preclinical results suggest, if directly applicable to humans, that the standard formulation and dosage of nitazoxanide is not effective in providing antiviral therapy for Covid-19.

Nitazoxanide

Antiviral drug

10.1101/2021.12.17.473113

Cite

Citations (2)