Human ivermectin exposure

International Journal of Current Microbiology and Applied Sciences, 2018

Journal of Mass Spectrometry, 2009

Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations. In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30-50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization-Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na + and K + ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 µg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed. There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI + MS/MS in samples originating from veterinary dosage forms.

Journal of Mass Spectrometry, 2009

Ivermectin is a semisynthetic macrocyclic lactone anthelmintic of the avermectin family derived from Streptomyces fermentation products. Avermectins are used as antiparasitic agents in domestic animals; although considered relatively safe, one must consider animal species, breed, weight, and age in dosage determinations.In January 2006, two canines were presented to the UK Livestock Disease Diagnostic Center after dying from suspected ivermectin overdoses [30–50 mg/kg body weight]. To confirm this clinical diagnosis we developed a rapid, sensitive semiquantitative ElectroSpray Ionization–Mass Spectrometry (ESI/MS) method for ivermectin in canine tissue samples. Pharmaceutical ivermectin contains two ivermectins differing by a single methyl group, and each compound forms interpretation-confounding adducts with tissue Na+ and K+ ions. We now report that ivermectin administration was clearly confirmed by comparison with standard and dosage forms of ivermectin, and simple proportionalities based on mass spectral intensity of respective molecular ions allowed semiquantitative estimates of injection site tissue concentrations of 20 and 40 µg/g tissue (wet weight) in these animals, consistent with the history of ivermectin administration and the clinical signs observed.There is a distinct need for both rapid detection and confirmation of toxic exposures in veterinary diagnostics, whether for interpretation of clinical cases antemortem or for forensic reasons postmortem. It is vital that interpreters of analytical results have appropriate guidance in the scientific literature and elsewhere so as to enable clear-cut answers. The method presented here is suitable for routine diagnostic work in that it allows rapid extraction of ivermectin from tissue samples, avoids the need for high-performance liquid chromatography and allows ready interpretation of the multiple ivermectin species seen by ESI+ MS/MS in samples originating from veterinary dosage forms. Copyright © 2008 John Wiley & Sons, Ltd.

Regulatory Toxicology and Pharmacology, 2007

Ivermectin was evaluated for its acute toxicity after single subcutaneous (s/c) administration by 'Acute Toxic Class' method as per OECD 423 and by conventional acute toxicity test using probit analysis in rats. 'Acute toxic class' method yielded LD 50 in category 2 i.e. between 5 and 50 mg/kg which was comparable with conventional method where it was found to be 51.5 mg/kg. Post mortem lesions were observed in the form of congestion of liver, which showed centrilobar necrosis and hemorrhages on histopathological analysis in both the methods. This study suggests, 'Acute Toxic Class' method may be used instead of conventional method to study acute toxicity of injectable preparations. Similarly the LD 50 of around 50 mg/kg indicated a wide margin of safety (250£) considering therapeutic dose of ivermectin as 200 g/kg.

International Journal for Parasitology, 2001

Pour-on formulations of endectocides are extensively used to treat and control systemic parasitic diseases in cattle, worldwide. The purpose of the present study was to investigate the influence of the natural licking behaviour of cattle on the plasma and faecal disposition of topically-administered ivermectin. Twelve Holstein cattle were given one single i.v. (200 µg/kg) and topical (500 µg/kg) administration of ivermectin at a 5-month interval. For the pour-on administration, the animals were allocated into two groups (n = 6): one control group (lickers) and one group where licking was prevented (non-lickers). Ivermectin plasma (total) clearance (270 ± 57.4 mL/kg/day) was very homogeneous among the 12 cattle. In contrast, major differences between lickers and non-lickers were observed following pour-on administration. Prevention of licking resulted in an extended terminal plasma half-life (363 ± 16.2 vs 154 ± 7.4 h in lickers) and in a lower and less variable systemic availability of ivermectin (19 ± 4.9 vs 33 ± 18.5% in lickers). More importantly, nearly 70% of the pour-on dose was recovered as parent drug in the faeces of lickers vs only 6.6% in non-lickers. Altogether, these results are consistent with an oral rather than percutaneous absorption of topical ivermectin in control animals, the non-systemically available fraction of ingested ivermectin providing a major contribution (80%) to the drug faecal output. The consequences of licking on the disposition of pour-on ivermectin are discussed in terms of environment, given the known ecotoxicity of this drug, and of cross-contamination. Animals licking themselves and each other could result in unexpected residues in edible tissues of untreated animals and in possible subtherapeutic drug concentrations, a factor in drug resistance. According to the Precautionary Principle, these considerations elicit concern over the use of topical drug formulations in cattle.

The Veterinary Journal, 2009

The pharmacokinetic properties of drugs are closely related to their pharmacological efficacy. The kinetics of ivermectin are characterised, in general terms, by a slow absorption process, a broad distribution in the organism, low metabolism, and slow excretion. The kinetics vary according to the route of administration, formulation, animal species, body condition, age, and physiological status, all of which contribute to differences in drug efficacy. Characterisation of ivermectin kinetics can be used to predict and optimise the value of the parasiticide effects and to design programmes for parasite control. This article reviews the pharmacokinetics of ivermectin in several domestic animal species.

Veterinary Sciences, 2022

Ivermectin has a wide number of many diverse functions. Certainly, it is irreplaceable for the treatment of parasitic pathologies in both human and veterinary medicine, and the latter represents the major field of its application. It has been called the “drug for the world’s poor” because of its role as a saviour for those living on the margins of society, in underdeveloped areas afflicted by devastating and debilitating diseases, such as Onchocerciasis and Lymphatic filariasis. It showed huge, unexpected potential as an antibacterial (Chlamydia trachomatis and mycobacteria), and it has antiviral and anti-inflammatory properties. The research line described here is placed right in the middle of the investigation on the impact of this drug as an antimicrobial and an immunomodulator. Being a drug widely employed for mass administration, it is mandatory to broaden the knowledge of its possible interaction with bacterial growth and its generation of antimicrobial resistance. Equally, it...

Jurnal Sain Peternakan Indonesia, 2020

Ivermectin belongs to macrocyclic lactones and is currently one of the most widely used antiparasitic drugs worldwide since its efficacy is well established. Ivermectin is highly active against a wide spectrum of nematode species, including most larvae, adult forms and also highly effective against many arthropod parasites of livestock animals. All ectoparasites are susceptible to ivermectin, including mites, ticks and biting flies. Toxicity to ivermectin is rarely found in livestock. Ivermectin poisoning is usually caused by mismanagement of medication by farmers in the form of excessive doses of ivermectin. The signs of toxicosis are mydriasis and depression, followed by ataxia, recumbency, and death. Symptomatic and supportive therapy can be given to suppress the effects of poisoning, however the most appropriate treatment is antidotes administration such as picrotoxin or physostigmine.

International Journal for Parasitology, 1996

Herd R. P., Stuns R. A. & Ashcrnft S. M. 1996. Persistence of ivermectin in plasma and faeces following treatment of cows with ivermectin sustained-release, pour-on or injectable formulations. International Jourdjiw Purasirology 26: 1087-1093. Sixteen young dairy cows were randomly allocated to 4 groups of 4 animals each: Group 1 cows were each given a single Ivomec SR Bolus; Group 2 cows were treated with the Ivomec Pour-on formulation; Group 3 cows were injected with the Ivomec Subcutaneous Injection; Group 4 cows were untreated controls. Blood and faecal samples were collected from all cows on the day before treatment and on days 1, 2, 3, 7, 14, 21, Zs, 35, 42 and 49 after treatment for HPLC determbration of plasma and faecal ivermectin concentrations. Group 1 (SR Bolus) cows bad mean (f S.D.) plasma ivermectin concentrations ranging from 5.6 f 1.8 pg I-' (p.p.b.) at 14 days to 11.0 f 4.7 pg I-' at 49 days. Faecal ivermectin concentrations were little changed from 4.0& 2.0 pg gg ' (p.p.m.) dry wt (dry weight) 10.5 f 0.2 /lg g-1 wet wt (wet weight)] at 14 days to 3.0 f 2.0 pg g-l dry wt (0.5 f 0.4 pg gg ' wet wt) at 49 days. Group 2 (Pour-on) cows showed a rapid rise in plasma concentrations to 32.9 f 15.7 pg I-' 2 days after treatment, followed by a gradual decline to 1.3hO.07 pg I-' at 2fl days. Faecal ivermectbr concentrations rose sharply to 18.5 h7.4 ,ug gg' dry wt (2.8rt 1.2 pg g-r wet wt) 2 days after treatment, then fell to 0.04*0.004~g g-1 dry wt (0.006*0.0004~g g-1 wet wt) at Zs days. Group 3 (Injection) cows also showed a rapid rise to an early plasma peak of 46.1 f 22.7 yg I-' 3 days after treatment, followed by a gradual decline to 1.3pg I-' at 35 days. Faecal ivermectin concentrations rose to 1.2+0.34~g g-r dry wt (0.2+0.05 pg gg ' wet wt) at 3 days, declining to O.Otl*O.OOOl fig g-' dry wt (0.01 f O.OOOll pg g-r wet wt) at Zs days. No ivermectin was detected in the plasma or faeces of Group 4 (Control) cows. Concentrations of ivermectin potentially toxic to dung-breeding or dung-feeding invertebrates were excreted for the duration of the study in dung of cows treated with the SR Bolus and for 28 days in the dung of cows treated with the Pour-on or injectable formulations.