Bioavailability of a commercial formulation of ivermectin after subcutaneous administration to sheep

Canga, Aránzazu González; Sahagún, Ana M.; Diez, M. José; Fernández, Nélida; Sierra, Matilde; García, José Alejos

doi:10.2460/ajvr.68.1.101

Cited by 18 publications

(9 citation statements)

References 30 publications

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“…The rapid time course of strychnine toxicity would agree with a single compartment distribution of the substance [ 32 – 34 ]. Ivermectin is known for its slow kinetics of distribution and excretion [ 16 ]; measurable amounts of the drug in humans and domestic animals are still found up to 17 days after administration of a single dose [ 16 , 35 , 36 ]. The ivermectin molecule is highly hydrophobic and is considered to accumulate extensively in fatty tissue which acts as a reservoir ( Figure 4(b) ), causing slow clearance from the body [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

In VivoProtection against Strychnine Toxicity in Mice by the Glycine Receptor Agonist Ivermectin

Maher

Radwan

Breitinger

2014

BioMed Research International

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The inhibitory glycine receptor, a ligand-gated ion channel that mediates fast synaptic inhibition in mammalian spinal cord and brainstem, is potently and selectively inhibited by the alkaloid strychnine. The anthelminthic and anticonvulsant ivermectin is a strychnine-independent agonist of spinal glycine receptors. Here we show that ivermectin is an effective antidote of strychnine toxicity in vivo and determine time course and extent of ivermectin protection. Mice received doses of 1 mg/kg and 5 mg/kg ivermectin orally or intraperitoneally, followed by an intraperitoneal strychnine challenge (2 mg/kg). Ivermectin, through both routes of application, protected mice against strychnine toxicity. Maximum protection was observed 14 hours after ivermectin administration. Combining intraperitoneal and oral dosage of ivermectin further improved protection, resulting in survival rates of up to 80% of animals and a significant delay of strychnine effects in up to 100% of tested animals. Strychnine action developed within minutes, much faster than ivermectin, which acted on a time scale of hours. The data agree with a two-compartment distribution of ivermectin, with fat deposits acting as storage compartment. The data demonstrate that toxic effects of strychnine in mice can be prevented if a basal level of glycinergic signalling is maintained through receptor activation by ivermectin.

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Section: Discussionmentioning

confidence: 99%

In VivoProtection against Strychnine Toxicity in Mice by the Glycine Receptor Agonist Ivermectin

Maher

Radwan

Breitinger

2014

BioMed Research International

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“…Durch eine systemische Bioverfügbarkeit von 50–60 % ergibt sich für diesen Stoff gemäß Biopharmaceutical Classification System (BCS) deshalb die Einordnung in die BCS-Klasse IV [ 14 , 15 ]. Durch die Anwendung von Ivermectin in gelöster Form lässt sich dessen systemische Bioverfügbarkeit deutlich erhöhen [ 16 ]. Deshalb wurde das Löslichkeitsverhalten des Arzneistoffs in relevanten Ölen untersucht, um eine Verarbeitung in gelöster Form auch gewährleisten, gleichzeitig aber auch die Quantität der Ölphase der Formulierung so gestalten zu können, dass die Stabilität der Emulsion erhalten bleibt.…”

Section: Materials Und Methodenunclassified

Entwicklung eines Ivermectin-haltigen Saftes als Magistralrezeptur für Kinder zur Therapie der Skabies

et al. 2021

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Zusammenfassung Hintergrund Zur Therapie der Skabies kann orales Ivermectin eingesetzt werden. Die Evidenz für einen sicheren und wirksamen Einsatz bei Kleinkindern im Einzelheilversuch ist erarbeitet worden und publiziert. Um eine körpergewichtsadaptierte Dosierung auch für Kinder zu gewährleisten, wurde ein Ivermectin-haltiger Saft als Magistralrezeptur entwickelt. Material und Methoden Da Ivermectin nicht als Reinsubstanz für die Rezeptur zur Verfügung steht, wurden wirkstoffhaltige Tabletten als Ausgangsmaterial für die Entwicklung benutzt. Die Formulierung wurde entsprechend pharmazeutischer, regulatorischer und gebrauchsorientierter Kriterien konzipiert. Zum Nachweis der chemischen Stabilität wurde eine HPLC(Hochleistungsflüssigkeitschromatographie)-Methode erarbeitet und validiert. Um die praktische Umsetzung zu erleichtern, wurden zudem Angaben zu geeigneten Packmitteln und zu Applikationshilfen erarbeitet, und die Rezeptur wurde taxiert. Ergebnisse Es konnte nachgewiesen werden, dass die finale Rezeptur stabil in der Apotheke hergestellt und über 3 Wochen gelagert werden kann. Es haben sich keine Bedenken bezüglich der Verträglichkeit des Rezeptursaftes ergeben. Die physikochemischen Eigenschaften und der Geschmack der Rezeptur ermöglichen den beabsichtigten Gebrauch als gut dosierbaren Saft für Kinder. Schlussfolgerung Die entwickelte Rezeptur entspricht den Anforderungen der Apothekenbetriebsordnung (§ 7 ApBetrO) und ermöglicht eine exakte, körpergewichtsadaptierte Dosierung von oralem Ivermectin bei Kleinkindern. Untersuchungen zur Pharmakokinetik am Menschen bzw. klinische Studien zum Nachweis der Verträglichkeit und/oder Wirksamkeit liegen für die Rezeptur nicht vor.

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“…The commercially available ivermectin preparations employ different vehicles that help in stabilizing the compound. It has been reported that the bioavailability of ivermectin varies according to the nature of vehicle [28]. Lifschitz et al .…”

Section: Impact Of Ivermectin Formulations On Its Pharmacokineticsmentioning

confidence: 99%

“…In this study, oleic acid was found to be an efficient vehicle for ivermectin due to its ability to enhance the solubility and transport by reducing the p-glycoprotein (P-gp)-mediated efflux of ivermectin. The composition of various formulations of ivermectin and their characteristic features is described in Table-1 [7,26,28,32-61]. Vehicles, such as oils, liposomes, and other microparticles, can reduce drug metabolism and can enhance the release of large quantities of the active form of the drug over a long period of time to the target site by altering its pharmacokinetics [62].…”

Section: Impact Of Ivermectin Formulations On Its Pharmacokineticsmentioning

confidence: 99%

Current therapeutic applications and pharmacokinetic modulations of ivermectin

et al. 2019

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Ivermectin is considered to be a wonder drug due to its broad-spectrum antiparasitic activity against both ectoparasites and endoparasites (under class of endectocide) and has multiple applications in both veterinary and human medicine. In particular, ivermectin is commonly used in the treatment of different kinds of infections and infestations. By altering the vehicles used in the formulations, the pharmacokinetic properties of different ivermectin preparations can be altered. Since its development, various vehicles have been evaluated to assess the efficacy, safety, and therapeutic systemic concentrations of ivermectin in different species. A subcutaneous route of administration is preferred over a topical or an oral route for ivermectin due to superior bioavailability. Different formulations of ivermectin have been developed over the years, such as stabilized aqueous formulations, osmotic pumps, controlled release capsules, silicone carriers, zein microspheres, biodegradable microparticulate drug delivery systems, lipid nanocapsules, solid lipid nanoparticles, sustained-release ivermectin varnish, sustained-release ivermectin-loaded solid dispersion suspension, and biodegradable subcutaneous implants. However, several reports of ivermectin resistance have been identified in different parts of the world over the past few years. Continuous use of suboptimal formulations or sub-therapeutic plasma concentrations may predispose an individual to resistance toward ivermectin. The current research trend is focused toward the need for developing ivermectin formulations that are stable, effective, and safe and that reduce the number of doses required for complete clinical cure in different parasitic diseases. Therefore, single-dose long-acting preparations of ivermectin that provide effective therapeutic drug concentrations need to be developed and commercialized, which may revolutionize drug therapy and prophylaxis against various parasitic diseases in the near future. The present review highlights the current advances in pharmacokinetic modulation of ivermectin formulations and their potent therapeutic applications, issues related to emergence of ivermectin resistance, and future trends of ivermectin usage. Keywords: ivermectin, ivermectin resistance, pharmacokinetic modulation, therapeutic applications.

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Bioavailability of a commercial formulation of ivermectin after subcutaneous administration to sheep

Cited by 18 publications

References 30 publications

In VivoProtection against Strychnine Toxicity in Mice by the Glycine Receptor Agonist Ivermectin

In VivoProtection against Strychnine Toxicity in Mice by the Glycine Receptor Agonist Ivermectin

Entwicklung eines Ivermectin-haltigen Saftes als Magistralrezeptur für Kinder zur Therapie der Skabies

Current therapeutic applications and pharmacokinetic modulations of ivermectin

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