A detailed pharmacokinetic analysis was performed with 47 children from Papua New Guinea with uncomplicated falciparum or vivax malaria treated with artesunate (ARTS) suppositories (Rectocaps) given in two doses of approximately 13 mg/kg of body weight 12 h apart. Following an intensive sampling protocol, samples were assayed for ARTS and its primary active metabolite, dihydroartemisinin (DHA), by liquid chromatography-mass spectrometry. A population pharmacokinetic model was developed to describe the data. Following administration of the first dose, the mean maximal concentrations of ARTS and DHA were 1,085 nmol/liter at 0.9 h and 2,525 nmol/liter at 2.3 h, respectively. The absorption half-life for ARTS was 2.3 h, and the conversion half-life (ARTS to DHA) was 0.27 h, while the elimination half-life of DHA was 0.71 h. The mean common volumes of distribution for ARTS and DHA relative to bioavailability were 42.8 and 2.04 liters/kg, respectively, and the mean clearance values relative to bioavailability were 6 and 2.2 liters/h/kg for ARTS and DHA, respectively. Substantial interpatient variability was observed, and the bioavailability of the second dose relative to that of the first was estimated to be 0.72. The covariates age, sex, and ␣-thalassemia genotype were not influential in the pharmacokinetic model development; but the inclusion of weight as a covariate significantly improved the performance of the model. An ARTS suppositories dose of 10 of 20 mg/kg is appropriate for use in children with uncomplicated malaria.

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The roots of B. capitata yielded the new compounds 5,8-dihydroxy-1-tigloylmethylnaphtho[2,3-c]furan-4,9-dione, 1-acetoxymethyl-8-hydroxynaphtho[2,3-c]furan-4,9-dione, and 1-acetoxymethyl-5,8-dihydroxynaphtho[2,3-c]furan-4,9-dione, in addition to the known compounds chrysophanol, 10,10'-chrysophanol bianthrone, 8-hydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione, 5,8-dihydroxy-1-hydroxymethylnaphtho[2,3-c]furan-4,9-dione, and 8-hydroxy-5-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione, or 5-hydroxy-8-methoxy-1-methylnaphtho[2,3-c]furan-4,9-dione. The new as well as the known isofuranonaphthoquinones showed antioxidant and weak antiplasmodial activities.

An improved method for the measurement of tissue metabolites associated with cellular energetic state by capillary electrophoresis is described. This method allows 17 compounds present in a mixture of standards to be determined simultaneously within 43 min with good reproducibility. ATP, ADP, AMP, UTP, IMP, inosine, hypoxanthine, creatine, phosphocreatine, UDP-galactose, NAD and NADH were detected in samples of either rat heart tissue or rat neonatal cardiomyocytes. This method can detect compounds at concentrations of 5 mm in samples. Recoveries for ATP and phosphocreatine added to cardiomyocyte samples were 99.4^2.1% and 103.1^3.3%, respectively (mean^SEM, n = 3). Our method has been comprehensively validated and is capable of measuring a wider range of tissue metabolites important in assessing cellular energy status than existing methods.Keywords: capillary electrophoresis; intracellular energy status; purine metabolism.The purine adenine nucleotide ATP is the primary source of cellular energy, and is essential for the maintenance of cellular energy homeostasis. Any change in cellular energy state is reflected by altered levels of purine nucleotides (ATP, ADP, AMP, IMP), purine nucleosides (inosine and adenosine), purine bases (hypoxanthine and xanthine) and uric acid, the end product of purine catabolism. Other important indicators of intracellular energy status include creatine and phosphocreatine (PCr) The aim of this study was to provide an efficient and reproducible method for quantitating the breakdown products of the nucleotide ATP, and a wide range of other compounds important in assessing intracellular energy and redox states. CE methods have an obvious advantage over HPLC and enzymatic methods, in that many compounds can be determined from just a few nanolitres of sample. To ensure sample reproducibility and sensitivity, it was essential that this method be rigorously optimized with respect to sample pH and running di-sodium tetraborate (borate) buffer concentration and pH. The reproducibility of this method was evaluated in terms of sample peak migration times and peak areas.In this paper we present a method for the simultaneous measurement of ATP, ADP, AMP, IMP, GTP, CTP, UTP, UDPglucose, UDP-galactose, creatine, PCr, adenosine, hypoxanthine, xanthine, inosine, lactate, NAD and uric acid within 40 min. In addition, ethanolic extraction of NADH from tissue samples made its measurement possible. To the best of our knowledge this CE method is the first capable of determining IMP, adenosine, hypoxanthine, UDP-galactose and NADH in tissue samples. EXPERIMENTAL PROCEDURES Preparation of standardsStandard solutions were prepared in a Tris-buffered Krebs± Henseleit solution (137 mm NaCl, 5.4 mm KCl, 1.0 mm NaH 2 PO 4 , 0.8 mm MgSO 4 , 2.0 mm CaCl 2 , 5.0 mm Tris and 5.5 mm glucose) supplemented with 10 mm verapamil and 50 mm NiCl 2 . Standards (100 mL) were deproteinized by the addition of 1.2 m perchloric acid (100 mL) before being centrifuged (10 000 g) for 10 min at 4 8C. The supernatant was removed an...