Practical HPLC methods for the quantitative determination of common antimalarials in Africa

Bell, David; Nyirongo, S.; Molyneux, Malcolm E.; Winstanley, PA; Ward, Stephen A.

doi:10.1016/j.jchromb.2006.10.020

Cited by 34 publications

(22 citation statements)

References 17 publications

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“…22 Ultraviolet detection of eluted peaks was performed at 340 nm. Chromatographic separation was carried out using the reversed-phase 150 mm x 4.6 mm Hypersil TM BDS C18 HPLC Columns (Thermo Fisher Scientific Inc., Waltham, Massachusetts, USA) with a 5 µm particle size.…”

Section: Methodsmentioning

confidence: 99%

Effect of Khat ( Catha edulis ) Use on the Bioavailability, Plasma Levels and Antimalarial Activity of Chloroquine

Issa

Al‐Habori

Chance

2016

SQUMJ

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abstract:Objectives: This study aimed to evaluate the effect of khat (Catha edulis) on chloroquine (CQ) bioavailability in healthy Yemeni adults and its effect on CQ plasma levels and parasite clearance among malaria patients. Methods: This study took place between January and April 2007 in Bajil and Sana'a, Yemen. Two CQ doses (600 mg each) were given to 15 healthy males on separate occasions; the first dose was followed by a khat-chewing session (phase one) while controls abstained from khat-chewing for the second (phase two). Additionally, 103 patients with Plasmodium falciparum-induced malaria, including both regular khat chewers (n = 57) and non-khat chewers (n = 46), were treated with CQ (25 mg/kg) over three days. Pharmacokinetic parameters were analysed among both controls and malaria patients. Parasite clearance was also investigated for the latter group. Results: The mean area under the concentration-time curve (AUC) was 2,108.9 versus 2,797.4 ng/hour/mL, mean peak plasma concentration (C max ) was 415.6 versus 508.7 ng/mL and mean time to reach C max was 3.8 versus 3.6 hours for controls in phase one versus phase two, respectively; both AUC and C max levels were significantly reduced by khat-chewing (P <0.050). For khat-versus non-khat-chewing malaria patients, mean plasma CQ concentrations were 266.4 ng/mL versus 427.5 ng/mL (P <0.001). Furthermore, CQ was effective in 71.7% and 75.4% of non-khat and khat-chewing malaria patients, respectively (P = 0.823). Conclusion: Khat-chewing was found to significantly reduce plasma CQ levels among healthy volunteers and malaria patients. While receiving CQ treatment, patients should be advised not to chew khat.

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Section: Methodsmentioning

confidence: 99%

Effect of Khat ( Catha edulis ) Use on the Bioavailability, Plasma Levels and Antimalarial Activity of Chloroquine

Issa

Al‐Habori

Chance

2016

SQUMJ

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“…Limited). The plasma concentrations of the two antimalarial drugs were determined at time points 0, 0.5, 2,4,8,12,18,24,36,48,72, and 96 h using a high-performance liquid chromatography assay (17), and noncompartmental pharmacokinetic analysis was undertaken to estimate the maximum concentration of the drugs in serum (C max ), time to maximum concentration (T max ), half-life (t 1/2 ), and area under the curve (AUC). To optimize estimation of clearance of parasitemia, blood sampling for qPCR was designed to be most intensive at the early stages after treatment (0, 0.5, 2, 4, 8, 12, 18, 24, 36, and 48 h).…”

Section: Methodsmentioning

confidence: 99%

Evaluating the Pharmacodynamic Effect of Antimalarial Drugs in Clinical Trials by Quantitative PCR

Marquart

Baker

O’Rourke

et al. 2015

Antimicrob Agents Chemother

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cThe ongoing development of new antimalarial drugs and the increasing use of controlled human malaria infection (CHMI) studies to investigate their activity in early-stage clinical trials require the development of methods to analyze their pharmacodynamic effect. This is especially so for studies where quantitative PCR (qPCR) is becoming the preferred method for assessing parasite clearance as the study endpoint. We report the development and validation of an analytic approach for qPCR-determined parasite clearance data. First, in a clinical trial with the licensed antimalarial combination sulfadoxine-pyrimethamine (S/P), qPCR data were collected from 12 subjects and used to determine qPCR replicate variability and to identify outliers. Then, an iterative analytic approach based on modeling the log-linear decay of parasitemia following drug treatment was developed to determine the parasite reduction ratio (PRR) and parasite clearance half-life, both measures of parasite clearance. This analytic approach was then validated with data from 8 subjects enrolled in a second study with the licensed antimalarial drug mefloquine. By this method, the PRR and parasite clearance half-lives for S/P and Mefloquine were determined to be 38,878 (95% confidence interval A critical determinant of the success of antimalarial chemotherapy is the speed of clearance of parasites from the blood of infected individuals. Indeed, this pharmacodynamic relationship represents one of the few clinically validated examples in antimicrobial chemotherapy. For example, the superiority of artemisinin antimalarials over comparator drugs, such as quinine, in terms of clinical endpoints can be attributed to the more rapid clearance of parasites from the blood following artemisinin combination chemotherapy (ACT) (1). Indeed, the increasing number of reports from the Greater Mekong Delta of slower clearance of Plasmodium falciparum from the blood following ACT forebodes worsening clinical outcomes (2-5).Quantification of parasitemia has generally relied on counting parasites on blood films. Advantages of this methodology include the ease of collection from finger prick, the low cost of consumables, and well-standardized methods. Additional useful information can be obtained from blood films, including infection with mixed parasite species, the presence of different life cycle stages, and the presence of malaria pigment in white cells. Disadvantages include the need for skilled microscopists who regularly undertake Quality Assurance Programs, the inferior sensitivity of microscopy compared to molecular techniques, and the time-consuming nature of reading multiple slides in the context of an ongoing clinical trial. Although quantitation of biomarkers of parasite biomass, such as histidine-rich protein 2, has some utility in measuring parasite biomass (6), it is not well suited for serial estimation of changes in parasite density in the context of drug treatment due to the kinetics of clearance of circulating parasite antigen differing from that of paras...

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“…Se hizo el mismo procedimiento en el día de control en el que se encontró reaparición de parasitemia, considerándose tal día como el día de falla terapéutica. Las muestras obtenidas se refrigeraron a 4 °C hasta el día de la medición de los niveles sanguíneos de cloroquina y de su metabolito principal, la desetilcloroquina, medidos por HPLC (27). Una concentración entre 70 y 90 ng/ml de cloroquina, más su metabolito principal, desetilcloroquina, es capaz de eliminar el total de formas asexuadas y sexuadas de P. vivax de la sangre (28,29).…”

Section: Cromatografía Líquida De Alta Resoluciónunclassified

Respuesta terapéutica del Plasmodium vivax a la cloroquina, en Riberalta, Guayaramerín y Yacuiba, Bolivia

Añez¹,

Navarro-Costa²,

Yucra³

et al. 2012

biomedica

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Practical HPLC methods for the quantitative determination of common antimalarials in Africa

Cited by 34 publications

References 17 publications

Effect of Khat ( Catha edulis ) Use on the Bioavailability, Plasma Levels and Antimalarial Activity of Chloroquine

Effect of Khat ( Catha edulis ) Use on the Bioavailability, Plasma Levels and Antimalarial Activity of Chloroquine

Evaluating the Pharmacodynamic Effect of Antimalarial Drugs in Clinical Trials by Quantitative PCR

Respuesta terapéutica del Plasmodium vivax a la cloroquina, en Riberalta, Guayaramerín y Yacuiba, Bolivia

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