Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus

Baraka, Omer Z.; Mahmoud, Babiker M.; Marschke, Charles K.; Geary, Timothy G.; Homeida, M; Williams, J. F.

doi:10.1007/s002280050131

Cited by 129 publications

(99 citation statements)

References 16 publications

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“…In such patients, plasma concentration of 52.0 ng/mL have been achieved in 5.2 hours, with an area under the curve over 48 hours of 2852 ng • h/mL. 32 Similar pharmacokinetics have been reported in healthy male volunteers receiving a 14-mg capsule of radiolabeled ivermectin. In these subjects, the mean T max was 6 hours, with a half-life of 11.8 hours.…”

supporting

confidence: 53%

The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells

Sharmeen

Škrtić

Sukhai

et al. 2010

Blood

110

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To identify known drugs with previously unrecognized anticancer activity, we compiled and screened a library of such compounds to identify agents cytotoxic to leukemia cells. From these screens, we identified ivermectin, a derivative of avermectin B1 that is licensed for the treatment of the parasitic infections, strongyloidiasis and onchocerciasis, but is also effective against other worm infestations. As a potential antileukemic agent, ivermectin induced cell death at low micromolar concentrations in acute myeloid leukemia cell lines and primary patient samples preferentially over normal hematopoietic cells. Ivermectin also delayed tumor growth in 3 independent mouse models of leukemia at concentrations that appear pharmacologically achievable. As an antiparasitic, ivermectin binds and activates chloride ion channels in nematodes, so we tested the effects of ivermectin on chloride flux in leukemia cells. Ivermectin increased intracellular chloride ion concentrations and cell size in leukemia cells. Chloride influx was accompanied by plasma membrane hyperpolarization, but did not change mitochondrial membrane potential. Ivermectin also increased reactive oxygen species generation that was functionally important for ivermectin-induced cell death. Finally, ivermectin synergized with cytarabine and daunorubicin that also increase reactive oxygen species production. Thus, given its known toxicology and pharmacology, ivermectin could be rapidly advanced into clinical trial for leukemia.

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supporting

confidence: 53%

The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells

Sharmeen

Škrtić

Sukhai

et al. 2010

Blood

110

View full text Add to dashboard Cite

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“…After an initial decrease, both groups showed a tendency for a second rise in plasma levels (mostly occurring between 6 and 12 h after the dose) suggesting an enterohepatic recycling of the drug (12).…”

Section: Absorptionmentioning

confidence: 94%

“…No differences in the elimination half-life were detected among healthy and onchocerciasis subjects (12). It was also suggested that the kinetics of ivermectin (its elimination halflife is around a day) were somewhat disconnected from its pharmacodynamics (antiparasitic events persisting for several months after a single dose of the drug) (11).…”

Section: Eliminationmentioning

confidence: 99%

The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review

Canga

Sahagún

Diez

et al. 2008

AAPS J

310

238

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“…Following oral administration, mean peak plasma concentration occurs approximately 4 h after dosing, a second peak at 6-12 h probably arising because of enterohepatic recycling of the drug, with the plasma half-life of ivermectin being around 12 h. [32][33][34] Dermal microfilarial loads are reduced by 78% within 2 days, and by some 98% within 2 weeks of treatment, remaining at extremely low levels for about 12 months. As lowest levels of microfilariae occur well after ivermectin administration, they are not necessarily killed when plasma drug levels are highest.…”

Section: The Present: a Puzzlementioning

confidence: 99%

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

2017

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Over the past decade, the global scientific community have begun to recognize the unmatched value of an extraordinary drug, ivermectin, that originates from a single microbe unearthed from soil in Japan. Work on ivermectin has seen its discoverer, Satoshi Ōmura, of Tokyo's prestigious Kitasato Institute, receive the 2014 Gairdner Global Health Award and the 2015 Nobel Prize in Physiology or Medicine, which he shared with a collaborating partner in the discovery and development of the drug, William Campbell of Merck & Co. Incorporated. Today, ivermectin is continuing to surprise and excite scientists, offering more and more promise to help improve global public health by treating a diverse range of diseases, with its unexpected potential as an antibacterial, antiviral and anti-cancer agent being particularly extraordinary.

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Ivermectin distribution in the plasma and tissues of patients infected with Onchocerca volvulus

Abstract: Infection with O. volvulus does not affect the pharmacokinetics of ivermectin, and filarial infected tissues and parasites themselves do take up the drug. There may be prolonged retention of ivermectin because of depot formation in fat tissue.

Cited by 129 publications

References 16 publications

The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells

The antiparasitic agent ivermectin induces chloride-dependent membrane hyperpolarization and cell death in leukemia cells

The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review

Ivermectin: enigmatic multifaceted ‘wonder’ drug continues to surprise and exceed expectations

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