Quantification of Tafenoquine and 5,6-Orthoquinone Tafenoquine by UHPLC-MS/MS in Blood, Plasma, and Urine, and Application to a Pharmacokinetic Study.

Analytical methods for the quantification of the new 8-aminoquinoline antimalarial tafenoquine (TQ) in human blood, plasma and urine, and the 5,6-orthoquinone tafenoquine metabolite (5,6-OQTQ) in human plasma and urine have been validated. The procedure involved acetonitrile extraction of samples followed by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Chromatography was performed using a Waters Atlantis T3 column with a gradient of 0.

Pharmacokinetics and Antimalarial Activity of Artesunate-Amodiaquine plus Methylene Blue in Healthy Volunteers.

High rates of artemisinin-based combination therapy (ACT) failures in the treatment of malaria in Southeast Asia have led to triple-drug strategies to extend the useful life of ACTs. In this study, we determined whether methylene blue [MB; 3,7-bis(dimethylamino)phenothiazin-5-ium chloride hydrate] alters the pharmacokinetics of artesunate-amodiaquine (ASAQ) and enhances the antimalarial activity of ASAQ. In an open-label, randomized crossover design, a single oral dose of ASAQ (200 mg AS/540 mg AQ) alone or with MB (325 mg) was administered to 15 healthy Vietnamese volunteers.

Efficacy and Pharmacokinetics of the 2-Aminomethylphenol Antimalarial JPC-3210 in the Monkey-Human Malaria Model.

Nonimmune monkeys infected with and were cured of their infections when treated with a single oral dose of 5 mg/kg and 10 mg/kg of the 2-aminomethylphenol, JPC-3210, respectively. Corresponding mean blood elimination half-lives of JPC-3210 were lengthy at 19.1 days and 20.

Comparison of the Pharmacokinetics and Ex Vivo Antimalarial Activities of Artesunate-Amodiaquine and Artemisinin-Piperaquine in Healthy Volunteers for Preselection Malaria Therapy.

The pharmacokinetics (PK) and ex vivo activity (pharmacodynamics [PD]) of two artemisinin combination therapies (ACTs) (artemisinin-piperaquine [ARN-PPQ] [Artequick] and artesunate-amodiaquine [ARS-AQ] [Coarsucam]) in healthy Vietnamese volunteers were compared following 3-day courses of the ACTs for the preselection of the drugs for falciparum malaria therapy. For PK analysis, serial plasma samples were collected from two separate groups of 22 volunteers after ACT administration. Of these volunteers, ex vivo activity was assessed in plasma samples from seven volunteers who received both ACTs.

Characterization of the Preclinical Pharmacology of the New 2-Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention.

The new 2-aminomethylphenol, JPC-3210, has potent antimalarial activity against multidrug-resistant lines, low cytotoxicity, and high efficacy against murine malaria. Here we report on the pharmacokinetics of JPC-3210 in mice and monkeys and the results of screening assays, including the inhibition of cytochrome P450 (CYP450) isozymes. In mice, JPC-3210 was rapidly absorbed and had an extensive tissue distribution, with a brain tissue-to-plasma concentration ratio of about 5.

The Spiroindolone KAE609 Does Not Induce Dormant Ring Stages in Plasmodium falciparum Parasites.

In vitro drug treatment with artemisinin derivatives, such as dihydroartemisinin (DHA), results in a temporary growth arrest (i.e., dormancy) at an early ring stage in Plasmodium falciparum This response has been proposed to play a role in the recrudescence of P.

Persistence and immunogenicity of chemically attenuated blood stage Plasmodium falciparum in Aotus monkeys.

Malaria is a disease caused by a protozoan of the Plasmodium genus and results in 0.5-0.7million deaths per year.

Population pharmacokinetics of phenytoin in critically ill children.

The objective was to study the population pharmacokinetics of bound and unbound phenytoin in critically ill children, including influences on the protein binding profile. A population pharmacokinetic approach was used to analyze paired protein-unbound and total phenytoin plasma concentrations (n = 146 each) from 32 critically ill children (0.08-17 years of age) who were admitted to a pediatric hospital, primarily intensive care unit.

Vincristine pharmacodynamics and pharmacogenetics in children with cancer: a limited-sampling, population modelling approach.

Background: Vincristine is a key component of many childhood cancer treatment regimens. Pharmacodynamic parameters such as clinical efficacy and toxicity may be influenced by polymorphisms of CYP3A.

Aim: The aim of this study was to document CYP3A5 genotype, vincristine pharmacokinetics (PK) and neurotoxicity profile for 50 children with cancer and determine whether, in a population of Australian children, the CYP3A5 genotype influenced the pharmacodynamics of vincristine as reflected by peripheral neurotoxicity.

Determination of risperidone and 9-Hydroxyrisperidone using HPLC, in plasma of children and adolescents with emotional and behavioural disorders.

A simple, rapid, selective, accurate and precise method is described for the determination of risperidone and its active metabolite, 9-hydroxyrisperidone, in plasma using a chemical derivative of risperidone (methyl-risperidone) as the internal standard. The sample workup involved a single-step extraction of 1 mL plasma, buffered to pH 10, with heptane-isoamyl alcohol (98:2 v/v), then evaporation of the heptane phase and reconstitution of the residue in mobile phase. HPLC separation was carried out at on C(18) column using a mobile phase of 0.

Stability of melatonin in an extemporaneously compounded sublingual solution and hard gelatin capsule.

This study examined the stability of melatonin in a 10-mg/mL oral sublingual solution stored at 4 deg C or 25 deg C and in 3-mg capsules stored at ambient (25 deg C; 60% relative humidity) and accelerated (40 deg C; 75% relative humidity) conditions over a period of 90 days. A sublingual solution of melatonin 10 mg/mL was preprared with glycerin, ethyl alcohol, stevia powder extract, and tutti-frutti flavor. Six identical solutions were prepared and stored in prescription amber glass bottles at 4 deg C or 25 deg C.