Defence Health

Department of Drug Evaluation

Mission

To support new drug discovery programs and optimise drug regimens for the treatment and protection of Australian Defence Force personnel against malaria infections. In support of this mission the department assesses the antimalarial activity of promising candidate drugs using parasitological tools and animal models. Pharmacokinetic and pharmacological studies of antimalarial drugs are carried out to optimise dose regimes for treatment and prophylaxis against malaria infections.

Current Research Projects

• Drug discovery screening of synthetic and natural products for intrinsic antimalarial activity using in vitro testing against Plasmodium falciparum isolates of varying levels of drug resistance (collaboration with Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington DC, USA; Jacobus Pharmaceutical Company, Inc, New Jersey, USA; Human Protection & Performance Division, Defence Science & Technology Organisation, Melbourne, Victoria).
• Uptake and stage specificity of piperaquine in different P. falciparum isolates, in vitro.
• Generation of new in vitro models: transfected P. falciparum parasite lines for antimalarial drug evaluation.
• Molecular characterisation for resistant markers of clinical field isolates of P. falciparum.
• In vivo antimalarial activity screening of natural products using rodent-Plasmodium berghei models with Eskitis Institute for Cell and Molecular Therapies, Griffith University, Brisbane Queensland (collaboration with Medicines for Malaria Venture (MMV)
• Preclinical development of 3rd generation antifols (collaboration with Jacobus Pharmaceutical Company, Inc.) for treatment and prophylaxis against malaria infections.
• Therapeutic efficacy and tolerability of dihydroartemisinin-piperaquine (Artekin), artemisinin-piperaquine (Artequick) and artesunate-amodiaquine (Coarsucam) for the treatment of Plasmodium falciparum malaria in central Vietnam (collaboration with Military Institute of Hygiene and Epidemiology, Hanoi, Vietnam and the Institute of Malariology, Parasitology and Entomology, Qui Nhon, Binh Dinh, Vietnam).
• Therapeutic efficacy, tolerability and pharmacokinetics of artesunate-azithromycin for the treatment of Plasmodium falciparum malaria (collaboration with Department of Infectious Disease, Military Hospital 175, Ho Chi Minh City, Vietnam).
• Pharmacokinetics of dihydroartemisinin-piperaquine (Artekin) and artesunate-azithromycin for the treatment of Plasmodium falciparum malaria (collaboration with Department of Infectious Disease, Military Hospital 108, Hanoi, Vietnam).

Collaborators

Australian

• School of Pharmacy, the University of Queensland
• Eskitis Institute for Cell and Molecular Therapies, Griffith University Brisbane Queensland
• Molecular Immunology, Queensland Institute of Medical Research
• Human Protection & Performance Division, Defence Science & Technology Organisation
• International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin,

International

• Division of Experimental Therapeutics, Walter Reed Army Institute of Research, USA
• Department of Immunology, Armed Forces Research Institute of Medical Sciences, Thailand
• Jacobus Pharmaceutical Company, USA
• Department of Infectious Disease, Military Hospital 108, Hanoi, Vietnam
• Department of Infectious Disease, Military Hospital 175, Ho Chi Minh City, Vietnam
• Institute of Malariology, Parasitology and Entomology, Qui Nhon, Binh Dinh, Vietnam
• Clinical Pharmacology Laboratory, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Thailand.
• Institute of Malariology, Parasitology and Entomology, Qui Nhon, Binh Dinh, Vietnam.
• Military Institute of Hygiene and Epidemiology, Hanoi, Vietnam.

 

Publications

2011

Xu M, Andrews KT, Birrell GW, Tran TL, Camp D, Davis RA, Quinn RJ. Psammaplysin H, a new antimalarial bromotyrosine alkaloid from a marine sponge of the genus Pseudoceratina. Bioorg Med Chem Lett. 2011; 21(2):846-8.

2010

Ovenden SP, Cobbe M, Kissell R, Birrell GW, Chavchich M, Edstein MD. Phenolic Glycosides with Antimalarial Activity from Grevillea "Poorinda Queen" J Nat Prod. 2010. Epub ahead of print.

2009

Nguyen DV, Nguyen QP, Nguyen ND, Le TT, Nguyen TD, Dinh DN, Nguyen TX, Bui D, Chavchich M, Edstein MD. Pharmacokinetics and ex vivo pharamcodynamic antimalarial activity of dihydroartemisinin-piperaquine in patients with uncomplicated falciparum malaria in Vietnam. Antimicrob Agents Chemother, 2009; 53 (8): 3534-7.

Obaldia N III, Kotecka BM, Edstein MD, Haynes RK, Fugmann B, Kyle DE, Rieckmann KH. Evaluation of artemisone combinations in Aotus monkeys infected with Plasmodium falciparum. Antimicrob Agents Chemother, 2009; 53 (8): 3592-4.

Thanh NX, Trung TN, Phone NC, Thien NX, Dai B, Shanks GD, Chavchich M, Edstein MD. Open label randomised comparison of dihydroartemisinin-piperaquine and artesunate-amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in central Vietnam. Trop Med Int Health, 2009; 14 (5): 504-11.

Chinh NT, Quang NN, Thanh NX, Dai B, Geue JP, Addison RS, Travers T, Edstein MD. Pharamcokinetics and bioequivalence evaluation of two fixed-dose tablet formulations of dihydroartemisinin and piperaquine in Vietnamese subjects. Antimicrob Agents Chemother, 2009; 53 (2): 828-31.

2008

Elmes NJ, Nasveld PE, Kitchener SJ, Kocisko DA, Edstein MD. The efficacy and tolerability of three different regimens of tafenoquine versus primaquine for post-exposure prophylaxis of Plasmodium vivax malaria in the Southwest Pacific. Trans R Soc Trop Med Hyg, 2008; 102 (11): 1095-101.

Wes W Sharrock, Rossarin Suwanarusk, Usa Lek-Uthai, Michael D Edstein, Varakorn Kosiavasee, Thomas Travers, Anchalee Jaidee, François Nosten, Bruce Russell. Plasmodium vivax Trophozoites Insensitive to Chloroquine. Malar J, 2008;7:94.

Johannes Nagelschmitz, Barbara Voith, Georg Wensing, Axel Roemer, Burkhard Fugmann, Richard K. Haynes, Barbara M. Kotecka, Karl H. Rieckmann, Michael D. Edstein. First Assessment in Humans of the Safety, Tolerability, Pharmacokinetics and Ex Vivo Pharmacodynamic Antimalarial Activity of the New Artemisinin Derivative, Artemisone. Antimicrob Agents Chemother, 2008; 52 (9): 3085-91.

Suwanarusk R, Chavchich M, Russell B, Jaidee A, Chalfein F, Barends M, Prasetyorini B, Kenangalem E, Piera KA, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN.  Pvmdr1 amplification and polymorphisms associated with multidrug resistant P. vivax.  J Infect Dis 2008, in press.

Nguyen Trong Chinh, Nguyen Ngoc Quang, Nguyen Xuan Thanh, Bui Dai, Thomas Travers, Michael D. Edstein.  Short Report: Pharmacokinetics of the antimalarial drug piperaquine in healthy Vietnamese subjects.  Am J Trop Med Hyg 2008, in press.

2007

Edstein MD, Nasveld PE, Kocisko DA, Kitchener SJ, Gatton ML, Rieckmann KH. Gender differences in gastrointestinal disturbances and plasma concentrations of tafenoquine in healthy volunteers after tafenoquine administration for post-exposure vivax malaria prophylaxis. Trans Roy Soc Trop Med Hyg 2007; 101: 226-230.

Ratcliff A, Siswantoro H, Kenangalem E, Wuwung M, Brockman A, Edstein MD, Laihad F, Ebsworth EP, Anstey NM, Tjitra E and Price RN.  Therapeutic response of multidrug-resistant Plasmodium falciparum and P. vivax to chloroquine and sulfadoxine–pyrimethamine in southern Papua, Indonesia. Trans Roy Soc Trop Med Hyg 2007; 101: 351-359.

Kitchener S, Nasveld P, Edstein MD.  Tafenoquine in the treatment of recurrent Plasmodium vivax malaria. Am J Trop Med Hyg 2007; 76: 494-496.

Charles BG, Blomgren A, Nasveld PE, Kitchener SJ, Jensen A, Gregory RM, Robertson B, Harris IE, Reid MP, Edstein MD.  Population pharmacokinetics of mefloquine in military personnel for prophylaxis against malaria infection during field deployment. Eur J Clin Pharmacol 2007; 63: 271-278.

Nguyen Van Hoang Dao, Bui Tri Cuong, Nguyen Dang Ngoa, Le Thi Thanh Thuy, Nguyen Duy The, Dinh Ngoc Duy, Bui Dai, Nguyen Xuan Thanh, Marina Chavchich, Karl H. Rieckmann, Michael D. Edstein. Vivax malaria: preliminary observations with a shorter course of treatment with artesunate plus primaquine. Trans Roy Soc Trop Med Hyg 2007; 101: 534-539.

Bruce G. Charles, Ann K. Miller,Peter E. Nasveld, Mark P. Reid, Ivor E. Harris, and Michael D. Edstein.  Population Pharmacokinetics of Tafenoquine during Malaria Prophylaxis in Healthy Subjects. Antimicrob Agents Chemother 2007; 51: 2709-2715.

Edstein MD, Kotecka BM, Ager AL, Smith KS, DiTusa CA, Diaz DS, Kyle, DE, Schiehser GA, Jacobus DP, Rieckmann KH, O’Neil MT.  Antimalarial pharmacodynamics and pharmacokinetics of a third-generation antifolate – JPC2056 – in cynomolgus monkeys using an in vivo-in vitro model. J Antimicrob Chemother 2007; 60: 811-818.

Suwanarusk R, Russell B, Chavchich M, Chalfein F, Kenangalem E, Kosaisavee V, Prasetyorini B, Piera KA, Barends M, Brockman A, Lek-Uthai U, Anstey NM, Tjitra E, Nosten F, Cheng Q, Price RN. Chloroquine resistant Plasmodium vivax: In vitro characterisation and association with molecular polymorphisms. PLoS ONE. 2007 Oct 31;2(10):e1089.

2006

Burns, M, Baker J, Auliff A, Gatton M, Edstein MD, Cheng Q. The efficacy of sulfadoxine-pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria in East Timor. Am J Trop Med Hyg 2006; 74: 361-366.

Bui Tri Cuong, Vu Quoc Binh, Bui Dai, Dinh Ngoc Duy, Claire M Lovell, Karl K Rieckmann, Michael D Edstein. Does food and gender affect the pharmacokinetics of primaquine in healthy Vietnamese subjects? Br J Clin Pharm 2006; 61: 682-689.

Elmes NJ, Bennett SM, Abdalla H, Carthew TL, Edstein MD. The pharmacokinetics of primaquine in healthy Australian male and female volunteers. Am J Trop Med Hyg 2006; 74: 951-952.

Haynes Fugmann B, Stetter J, Rieckmann K, Heilmann HD, Chan HW, Cheung MK, Lam WL, Wong HN, Croft SL, Vivas L, Rattray L, Stewart L, Peters W, Robinson BL, Edstein MD, Kotecka B, Kyle DE, Gerisch M, Radtke M, Schmuck G, Steinke W, Wollborn U, Schmeer K, Romer A. Artemisone – A highly active antimalarial drug of the artemisinin class. Angew Chem 2006; 45: 1-8.

21 September, 2011