Treatment of Pinworm Infections With Reduced Single Dose of Pyrvinium Pamoate

Beck, J. Walter

doi:10.1001/jama.1964.03070060121016

Cited by 10 publications

(6 citation statements)

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“…It is a small lipophilic compound, with multiple amine groups and a positive charge at physiologic pH. In a series of articles between 1947 and 1959 describing the anthelminthic (targeting parasitic worms) activity of cyanine dyes, pyrvinium chloride salt and pyrvinium pamoate (also known as pyrvinium embonate, see Figure 1 ) were noted to be effective anthelmintics [ 11 , 12 , 13 , 14 ]. It was subsequently determined that pyrvinium pamoate (PP) had similar efficacy and less clinical toxicity than pyrvinium chloride [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

“…The reduced toxicity of pyrvinium pamoate compared to pyrvinium chloride was likely due to reduced water solubility, which likely leads to decreased systemic gastrointestinal absorption [ 16 ]. PP thus became one of the primary treatments for various worm infestations for both human and veterinary use [ 14 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. With the advent of newer anti-parasitic agents, the utilization of PP as an anthelmintic in the United States gradually declined in the 1970s–1980s [ 24 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug

Schultz

2022

Biomedicines

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Pyrvinium, a lipophilic cation belonging to the cyanine dye family, has been used in the clinic as a safe and effective anthelminthic for over 70 years. Its structure, similar to some polyaminopyrimidines and mitochondrial-targeting peptoids, has been linked with mitochondrial localization and targeting. Over the past two decades, increasing evidence has emerged showing pyrvinium to be a strong anti-cancer molecule in various human cancers in vitro and in vivo. This efficacy against cancers has been attributed to diverse mechanisms of action, with the weight of evidence supporting the inhibition of mitochondrial function, the WNT pathway, and cancer stem cell renewal. Despite the overwhelming evidence demonstrating the efficacy of pyrvinium for the treatment of human cancers, pyrvinium has not yet been repurposed for the treatment of cancers. This review provides an in-depth analysis of the history of pyrvinium as a therapeutic, the rationale and data supporting its use as an anticancer agent, and the challenges associated with repurposing pyrvinium as an anti-cancer agent.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug

Schultz

2022

Biomedicines

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“…Based on the efficacy of this drug against C. parvum and the distantly related malaria parasite, P. falciparum, we postulate that pyrvinium will be effective against other Cryptosporidium species of medical and veterinary importance, including C. hominis and C. andersoni, respectively. Although trials with humans will be necessary to determine the minimum effective dose and tolerable doses, the safety of pyrvinium for treatment of humans has already been established (4,27), which will significantly reduce the time and costs required for clinical trials. Based on these results, we believe that pyrvinium pamoate is a potential drug candidate for the treatment of cryptosporidiosis in immunocompetent and also immunocompromised individuals, for whom no effective therapy is currently approved.…”

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confidence: 99%

Efficacy of Pyrvinium Pamoate against Cryptosporidium parvum Infection In Vitro and in a Neonatal Mouse Model

Downey¹,

Chong

Graczyk

et al. 2008

Antimicrob Agents Chemother

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No effective approved drug therapy exists for Cryptosporidium infection of immunocompromised patients.Here we investigated the nonabsorbed anthelmintic drug pyrvinium pamoate for inhibition of the growth of the intestinal protozoan parasite Cryptosporidium parvum. The concentration of pyrvinium that effected 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was 354 nM. For comparison, in the same assay, 50% growth inhibition was obtained with 711 M paromomycin or 27 M chloroquine. We used a neonatal mouse model to measure the anti-Cryptosporidium activity of pyrvinium pamoate in vivo. Beginning 3 days after infection, pyrvinium at 5 or 12.5 mg/kg of body weight/day was administered to the treatment group mice for 4 or 6 consecutive days. Nine days after infection, the mice were sacrificed, and drug efficacy was determined by comparing the numbers of oocysts in the fecal smears of treated versus untreated mice. The intensities of trophozoite infection in the ileocecal intestinal regions were also compared using hematoxylin-and-eosin-stained histological slides. We observed a >90% reduction in infection intensity in pyrvinium-treated mice relative to that in untreated controls, along with a substantial reduction in tissue pathology. Based on these results, pyrvinium pamoate is a potential drug candidate for the treatment of cryptosporidiosis in both immunocompetent and immunocompromised individuals.Cryptosporidium is an important apicomplexan protozoan pathogen that contributes significantly to diarrheal disease in both humans and animals throughout the world (9, 10, 21). In immunocompetent hosts, infections are generally restricted to the intestinal epithelium, causing an acute, self-limiting gastroenteritis. However, in AIDS patients and other immunocompromised individuals, infection can result in life-threatening, chronic diarrhea and may spread to extraintestinal locations (16,26). Although the efficacies of numerous antimicrobial agents against Cryptosporidium infection have been tested using animal and cell culture models, there is currently no reliably effective therapeutic for the treatment of chronic cryptosporidiosis in immunocompromised patients (30).Recently, nitazoxanide (NTZ), a nitrothiazole benzamide, was approved by the FDA for the treatment of cryptosporidiosis in immunocompetent adults and children aged Ͼ1 year (2). However, while clinical studies are ongoing, the efficacy of NTZ for the treatment of Cryptosporidium infection in immunocompromised patients has not yet been demonstrated (1). A 50% inhibitory concentration (IC 50 ) of 3.8 M has been reported for NTZ in cell culture (12). In a neonatal mouse model, oral administration of NTZ at 150 mg/kg of body weight reduced oocyst output to less than 5% of that seen in controls (6); however, NTZ at 100 or 200 mg/kg was ineffective at reducing parasite burdens in a SCID mouse model (24).Prior to the FDA approval of NTZ as an anti-Cryptosporidium therapeutic, the glycoside antibiotic paromomyc...

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“…This was confirmed by BIGUET et al (1952), BUMBALO et al (1958) and many other authors. KOMIYA et al (1962), BECK (1964), andNISHI-MURA et al (1965) obtained similar good results after the administration of a single 1-to 2-mg/kg dose. 7.5 mg pyrvinium pamoate corresponds to 5 mg pyrvinium base.…”

Section: Mass Treatmentmentioning

confidence: 76%

Chemotherapy of Gastrointestinal Nematodiasis in Man

Janssens¹

1985

Chemotherapy of Gastrointestinal Helminths

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Treatment of Pinworm Infections With Reduced Single Dose of Pyrvinium Pamoate

Cited by 10 publications

References 0 publications

Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug

Pyrvinium Pamoate: Past, Present, and Future as an Anti-Cancer Drug

Efficacy of Pyrvinium Pamoate against Cryptosporidium parvum Infection In Vitro and in a Neonatal Mouse Model

Chemotherapy of Gastrointestinal Nematodiasis in Man

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