High-Pressure Liquid Chromatographic Analysis of Eflornithine in Serum

Cohen, Jordan L.; Ko, Richard J.; Lo, Alice T.L.; Shields, Mark D.; Gilman, Thomas M.

doi:10.1002/jps.2600780208

Cited by 21 publications

(11 citation statements)

References 6 publications

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“…The age groups at highest risk for rhodesiense HAT are active, working-age groups who are most likely to venture to tsetse habitats, for example to collect firewood or honey, to herd cattle, to farm in peripheral areas and to fish and hunt, and rangers in natural protected areas (116,117). The burden of infection on society as a whole is therefore high, affecting the income-generating capacity of families, apart from the effect at individual level.…”

Section: Rhodesiense Human African Trypanosomiasismentioning

confidence: 99%

“…The relapse rate for first-stage gambiense HAT observed after pentamidine treatment is, however, < 5% (101,116). However, for second-stage gambiense HAT, since NECT is used as the first-line treatment in about 98% of patients, the relapse rate is < 2% (117, 118).…”

Section: Treatment Outcome Assessmentmentioning

confidence: 99%

“…Specific HPLC methods have been described for the determination of eflornithine (116)(117)(118)(119)(120)(121) and specifically for its enantionmers (122).…”

Section: Eflornithinementioning

confidence: 99%

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6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors

et al. 2015

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From a whole-organism high throughput screen of approximately 87000 compounds against Trypanosoma brucei brucei, we recently identified eight new unique compounds for the treatment of human African trypanosomiasis. In an effort to understand the structure−activity relationships around these compounds, we report for the first time our results on a new class of trypanocides, the pyrazine carboxamides. Attracted by the low molecular weight (270 g•mol −1 ) of our starting hit (9) and its potency (0.49 μM), the SAR around the core was explored, leading to compounds having an EC 50 as low as 25 nM against T. b. brucei and being more than 1500 times less toxic against mammalian L6 and HEK293 cell lines. The most potent compounds in the series were exquisitely selective for T. brucei over a panel of other protozoan parasites, showing an excellent correlation with the human infective parasite Trypanosoma brucei rhodesiense, the most potent compound (65) having an EC 50 of 24 nM. The compounds are highly drug-like and are able to penetrate the CNS, their only limitation currently being their rate of microsomal metabolism. To that effect, efforts to identify potential metabolites of selected compounds are also reported.

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Section: Rhodesiense Human African Trypanosomiasismentioning

confidence: 99%

Section: Treatment Outcome Assessmentmentioning

confidence: 99%

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6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors

et al. 2015

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“…HPLC analysis of DFMO in tissues-DFMO in lung tissues and serum was quantified by HPLC following derivatization with dansyl chloride by a modification of the procedure of Cohen et al (16). DMFO was assayed in lung by first weighing each lung.…”

Section: Ultrasonic Transducers-mentioning

confidence: 99%

High-Frequency Ultrasonic Atomization for Drug Delivery to Rodent Animal Models—optimal Particle Size for Lung Inhalation of Difluoromethyl Ornithine

Zhang

Fandrey

Naqwi

et al. 2008

Experimental Lung Research

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A high (8 MHz) and low (1.7 MHz) frequency ultrasonic transducer were compared for delivering aerosols to mouse lung. The aerosol concentration (mass of dry particles/volume of air) rose nonlinearly with solution concentration of difluoromethyl ornithine for both transducers. The particle size was linear with the cube root of the solution concentration, and the slope of the low frequency transducer was eight times greater than that of the high frequency transducer. The deposition fraction assessed by the assayed mass in the lung relative to the calculated inhaled mass was found to decline exponentially with particle size. The lower frequency transducer provided a higher dose despite a lower deposition fraction, but the high frequency transducer was more efficient and provides a more selective deposition in the lower respiratory tract while operating with significantly less demands on aerosol drying.

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“…It is caused by Trypanosoma brucei gambienze, African trypanosomiasis [1,2]. DFMO is effective in the treatment of facial hirsutism [3] as well as in African trypanosomiasis, also known as sleeping sickness [2].…”

Section: Introductionmentioning

confidence: 99%