Attempt to Correlate Urine Arsenic Excretion with Clinical Course during Melarsoprol Therapy of Patients with Rhodesian Trypanosomiasis

Harrison, Shannon M.; Harris, Richard W.; Bales, James D.

doi:10.4269/ajtmh.1997.56.632

Cited by 6 publications

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“…There are currently four treatments in use for the two different stages of human African trypanosomiasis (Table 3), all of which exhibit substantial toxicities: pentamidine, suramin, melarsoprol, and nifurtimox plus eflornithine. Clinical PK studies were identified for three of these treatments: pentamidine [28, 29], melarsoprol [30–33], and eflornithine [34–36]. Additionally, PK studies were found for fexinidazole, a drug currently still in late-phase clinical development [37, 38].…”

Section: Resultsmentioning

confidence: 99%

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Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

Verrest

Dorlo

2016

Clin Pharmacokinet

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IntroductionNeglected tropical diseases (NTDs) affect more than one billion people, mainly living in developing countries. For most of these NTDs, treatment is suboptimal. To optimize treatment regimens, clinical pharmacokinetic studies are required where they have not been previously conducted to enable the use of pharmacometric modeling and simulation techniques in their application, which can provide substantial advantages.ObjectivesOur aim was to provide a systematic overview and summary of all clinical pharmacokinetic studies in NTDs and to assess the use of pharmacometrics in these studies, as well as to identify which of the NTDs or which treatments have not been sufficiently studied.MethodsPubMed was systematically searched for all clinical trials and case reports until the end of 2015 that described the pharmacokinetics of a drug in the context of treating any of the NTDs in patients or healthy volunteers.ResultsEighty-two pharmacokinetic studies were identified. Most studies included small patient numbers (only five studies included >50 subjects) and only nine (11 %) studies included pediatric patients. A large part of the studies was not very recent; 56 % of studies were published before 2000. Most studies applied non-compartmental analysis methods for pharmacokinetic analysis (62 %). Twelve studies used population-based compartmental analysis (15 %) and eight (10 %) additionally performed simulations or extrapolation. For ten out of the 17 NTDs, none or only very few pharmacokinetic studies could be identified.ConclusionsFor most NTDs, adequate pharmacokinetic studies are lacking and population-based modeling and simulation techniques have not generally been applied. Pharmacokinetic clinical trials that enable population pharmacokinetic modeling are needed to make better use of the available data. Simulation-based studies should be employed to enable the design of improved dosing regimens and more optimally use the limited resources to effectively provide therapy in this neglected area.Electronic supplementary materialThe online version of this article (doi:10.1007/s40262-016-0467-3) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

“…However the PK–PD relationships for melarsoprol remain unclear: melarsoprol PK parameters and CSF/plasma exposure were not significantly different in refractory compared with cured patients [32] and arsenic urinary excretion was not predictive of either toxicity or efficacy of melarsoprol [30]. …”

Section: Resultsmentioning

confidence: 99%

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

Verrest

Dorlo

2016

Clin Pharmacokinet

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“…Most medicinal uses of arsenic compounds were based on their toxic nature. At present, arsenic is used for the treatment of trypanosomiasis (sleeping sickness) (Harrison, Harris, and Bales 1997; Médecins Sans Frontières 2006), and recently emerged as an effective treatment for acute promyelocytic leukemia (Zhang et al 2010) as well as other types of human neoplasia (Miller et al 2002; Han et al 2004; Hu et al 2005; Shao et al 2005; Cheng, Chang, and Tsou 2006; Luo et al 2006; Ai, Lu, and Qin 2006; Cheung, Chu, and Kwong 2007).…”

Section: Introductionmentioning

confidence: 99%

Effect of Sodium Arsenite on Mouse Skin Carcinogenesis

Palmieri

Molinari

2015

Toxicol Pathol

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Arsenic is carcinogenic in human beings, and environmental exposure to arsenic is a public health issue that affects large populations worldwide. Thus, studies are needed to determine the mode of action of arsenic and prevent harmful effects arising from arsenic intake. The present study assessed the influence of sodium arsenite (As 3þ ) on potentially carcinogenic processes that are either pre-existing or concomitant with chronic intake of water containing As 3þ . Experiments using SENCAR mice were designed to evaluate the effect of chronic administration of As 3þ (2, 20, or 200 mg of As 3þ /L) in drinking water that overlapped to varying degrees with a 2-stage carcinogenesis protocol carried out over 9 months. The results showed a time-dependent pattern. During early stages of carcinogenesis (6-12 weeks), animals exposed to As 3þ and the carcinogenesis protocol showed increased numbers of tumors compared to control animals. During late carcinogenesis (16-30 weeks), the number of tumors stabilized to below control values, but the tumors showed increased malignancy. These findings indicate that the outcomes of the 2-stage skin carcinogenesis protocol are modified by the presence of arsenite in drinking water, which increases the rate of carcinoma development.

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The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human

Arya,

Bhardwaj,

Karn

2023

Environmental Science and Engineering

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Attempt to Correlate Urine Arsenic Excretion with Clinical Course during Melarsoprol Therapy of Patients with Rhodesian Trypanosomiasis

Cited by 6 publications

References 0 publications

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

Lack of Clinical Pharmacokinetic Studies to Optimize the Treatment of Neglected Tropical Diseases: A Systematic Review

Effect of Sodium Arsenite on Mouse Skin Carcinogenesis

The Effects of Arsenic Exposure on Neurological and Cognitive Dysfunction in Human

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