Eflornithine Treatment of Pneumocystis carinii Pneumonia in AIDS

Gilman, Thomas M.; Paulson, Yana J.; Boylen, C. Thomas; Heseltine, Peter N. R.; Sharma, Om P.

doi:10.1001/jama.1986.03380160055013

Cited by 22 publications

(1 citation statement)

References 2 publications

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“…DFMO is used to treat the second stage of African trypanosomiasis (sleeping sickness). In addition, DFMO is also used to treat opportunistic infections with Pneumocystis carinii pneumonia , a form of pneumonia found in people with a weak immune system suffering from conditions such as acquired immunodeficiency syndrome (AIDS) . It has also been explored as chemopreventive agent in cancer therapy with minor success .…”

Section: Introductionmentioning

confidence: 99%

Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source

Köckinger

Hone

Gutmann

et al. 2018

Org. Process Res. Dev.

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The development of a scalable telescoped continuous flow procedure for difluoromethylation of a protected amino acid with fluoroform (CHF 3 , R-23) gas and subsequent high temperature deprotection to provide eflornithine, an important Active Pharmaceutical Ingredient (API), is described. Eflornithine is used for the treatment of sleeping sickness and hirsutism, and it is on the World Health Organization's list of essential medicines. Fluoroform is produced in large quantities as a side product in the manufacture of polytetrafluoroethylene (PTFE, Teflon). Fluoroform is an ozone-benign and nontoxic gas, but its release into the environment is forbidden under the Kyoto protocol owing to its high global warming potential. The existing manufacturing route to eflornithine uses chlorodifluoromethane (CHClF 2 , R-22) which will be phased out under the Montreal protocol; therefore, the use of the fluoroform presents a viable cost-effective and more sustainable alternative. The process parameters and equipment setup were optimized on laboratory scale for the two reaction steps to improve product yield and scalability. The telescoped flow process utilizing fluoroform gas was operated for 4 h to afford the target molecule in 86% isolated yield over two steps with a throughput of 24 mmol/h.

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Section: Introductionmentioning

confidence: 99%

Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source

Köckinger

Hone

Gutmann

et al. 2018

Org. Process Res. Dev.

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A Meta-analysis of Salvage Therapy for Pneumocystis carinii Pneumonia

Smego¹,

Nagar²,

Maloba³

et al. 2001

Arch Intern Med

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Eflornithine for the Treatment of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome: A Preliminary Review

Sahai

Berry

1989

Pharmacotherapy

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Pneumocystis carinii pneumonia (PCP) is the most common opportunistic infection in patients with acquired immunodeficiency syndrome (AIDS). Eflornithine is an antiprotozoal agent active against P. carinii. It acts by inhibiting ornithine decarboxylase, an enzyme that is essential for cellular function. The drug is initially administered intravenously, followed by oral therapy. Eflornithine has been used on a compassionate basis in AIDS patients with PCP who were intolerant of or unresponsive to traditional agents. Overall, the response rate has been about 35%; however, conclusions are difficult to make since patients had different stages of disease and received treatment for varying periods of time. Side effects include depression of bone marrow function, diarrhea, hearing loss, seizures, alterations in liver function tests, and rash. While the need for safer and more efficacious antipneumocystis drugs grows, widespread use of seemingly promising agents should be based on well-conducted clinical trials.

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Eflornithine Treatment of Pneumocystis carinii Pneumonia in AIDS

Cited by 22 publications

References 2 publications

Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source

Scalable Continuous Flow Process for the Synthesis of Eflornithine Using Fluoroform as Difluoromethyl Source

A Meta-analysis of Salvage Therapy for Pneumocystis carinii Pneumonia

Eflornithine for the Treatment of Pneumocystis carinii Pneumonia in Patients with the Acquired Immunodeficiency Syndrome: A Preliminary Review

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