Walter C. Taylor
Mahidol University
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Malaria Journal | 2009
Kasia Stepniewska; Walter C. Taylor; Sodiomon B. Sirima; Espérance Ouédraogo; Alphonse Ouédraogo; Adama Gansané; Julie A. Simpson; Caroline C. Morgan; Nicholas J. White; Jean-René Kiechel
BackgroundPharmacokinetic (PK) data on amodiaquine (AQ) and artesunate (AS) are limited in children, an important risk group for malaria. The aim of this study was to evaluate the PK properties of a newly developed and registered fixed dose combination (FDC) of artesunate and amodiaquine.MethodsA prospective population pharmacokinetic study of AS and AQ was conducted in children aged six months to five years. Participants were randomized to receive the new artesunate and amodiaquine FDC or the same drugs given in separate tablets. Children were divided into two groups of 70 (35 in each treatment arm) to evaluate the pharmacokinetic properties of AS and AQ, respectively. Population pharmacokinetic models for dihydroartemisinin (DHA) and desethylamodiaquine (DeAq), the principal pharmacologically active metabolites of AS and AQ, respectively, and total artemisinin anti-malarial activity, defined as the sum of the molar equivalent plasma concentrations of DHA and artesunate, were constructed using the non-linear mixed effects approach. Relative bioavailability between products was compared by estimating the ratios (and 95% CI) between the areas under the plasma concentration-time curves (AUC).ResultsThe two regimens had similar PK properties in young children with acute malaria. The ratio of loose formulation to fixed co-formulation AUCs, was estimated as 1.043 (95% CI: 0.956 to 1.138) for DeAq. For DHA and total anti-malarial activity AUCs were estimated to be the same. Artesunate was rapidly absorbed, hydrolysed to DHA, and eliminated. Plasma concentrations were significantly higher following the first dose, when patients were acutely ill, than after subsequent doses when patients were usually afebrile and clinically improved. Amodiaquine was converted rapidly to DeAq, which was then eliminated with an estimated median (range) elimination half-life of 9 (7 to 12) days. Efficacy was similar in the two treatments groups, with cure rates of 0.946 (95% CI: 0.840–0.982) in the AS+AQ group and 0.892 (95% CI: 0.787 – 0.947) in the AS/AQ group. Four out of five patients with PCR confirmed recrudescences received AQ doses < 10 mg/kg. Both regimens were well tolerated. No child developed severe, post treatment neutropaenia (<1,000/μL). There was no evidence of AQ dose related hepatotoxicity, but one patient developed an asymptomatic rise in liver enzymes that was resolving by Day-28.ConclusionThe bioavailability of the co-formulated AS-AQ FDC was similar to that of the separate tablets for desethylamodiaquine, DHA and the total anti-malarial activity. These data support the use this new AS-AQ FDC in children with acute uncomplicated falciparum malaria.
Phytochemistry | 1988
Patoomratana Tuchinda; Jinda Udchachon; Kanjai Khumtaveeporn; Walter C. Taylor; Lutz M. Engelhardt; Allan H. White
Abstract From the tubers of Eulophia nuda six phenanthrene derivatives have been isolated: 9,10-dihydro-2,5-dimethoxyphenanthrene-1,7-diol, 9,10-dihydro-4-methoxyphenanthrene-2,7-diol, 1,5-dimethoxyphenanthrene-2,7-diol, 1,5,7,-trimethoxyphenanthrene-2,6-diol, 5,7-dimethoxyphenanthrene-2,6-diol and 4,4′,8,8′-tetramethoxy [1,1′-biphenanthrene]-2,2′,7,7′-tetrol. 4-Hydroxybenzaldehyde and 4-hydroxybenzyl alcohol were also isolated. The structures were assigned by spectroscopic methods and the structure of 9, 10-dihydro-2,5-dimethoxyphenanthrene- 1,7-diol was also determined by a single-crystal X-ray structure analysis of its acetate derivative.
Phytochemistry | 1991
Patoomratana Tuchinda; Jinda Udchachon; Vichai Reutrakul; Thawatchai Santisuk; Walter C. Taylor; Norman R. Farnsworth; John M. Pezzuto; A. Douglas Kinghorn
Abstract From leaves and branches of Melodorum fruticosum , five butenolides have been isolated: (4 Z )-6-acetoxy-7-benzoyloxy-2,4-heptadien-4-olide, (4 E )-6-acetoxy-7-benzoyloxy-2,4-heptadien-4-olide, (4 Z )-7-benzoyloxy-6-hydroxy-2,4-heptadien-4-olide, (4 E )-7-benzoyloxy-6-hydroxy-2,4-heptadien-4-olide and (4 Z )-6-benzoyloxy-7-hydroxy-2,4-heptadien-4-olide. In addition, two known flavonoids (chrysin, pinocembrin) and benzoic acid were isolated. All butenolides showed cytotoxic activities in several tumour cell lines. The structures of the isolated compounds were elucidated by spectroscopic methods.
Australian Journal of Chemistry | 2006
Anthony C. Willis; Patrick D. O'Connor; Walter C. Taylor; Lewis N. Mander
The X-ray crystal structures have been determined for three alkaloids isolated from the bark of the rainforest tree Galbulimima belgraveana, namely himbosine, himandrine, and himgaline, thereby allowing the absolute configuration to be established for these three compounds and 15 further alkaloids from this source.
Australian Journal of Chemistry | 2001
Phan Tong Son; Phan Minh Giang; Walter C. Taylor
A new ent-kaurane diterpenoid, ent-7β-hydroxy-15-oxokaur-16-en-18-yl acetate (1), has been isolated from the leaves of Croton tonkinensis Gagnep. (Euphorbiaceae). Its structure was established mainly by 1 H and 13 C nuclear magnetic resonance (n.m.r.) spectroscopy.
Journal of Natural Products | 1987
Wilawan Mahabusarakam; Pichaet Wiriyachitra; Walter C. Taylor
Planta Medica | 1994
Pornpipat na Pattalung; Weera Thongtheeraparp; Pichaet Wiriyachitra; Walter C. Taylor
Planta Medica | 2006
Wilawan Mahabusarakam; Kunnika Kuaha; Prapon Wilairat; Walter C. Taylor
Journal of Natural Products | 2003
Vatcharin Rukachaisirikul; Mayuree Kamkaew; Dusadee Sukavisit; Souwalak Phongpaichit; Prakart Sawangchote; Walter C. Taylor
Planta Medica | 2003
Vatcharin Rukachaisirikul; Phanruethai Pailee; Assdhawut Hiranrat; Patoomratana Tuchinda; Chalobon Yoosook; Jittra Kasisit; Walter C. Taylor; Vichai Reutrakul