Influence of verapamil on pharmacokinetics and transplacental transfer of ivermectin in sheep

Pérez, R.; Palma, Cristina; Núñez, M. J.; Urrutia, Pedro; Salazar, Aurelio; Morales, Leonardo Fabio; Vera, Daniela B.; Cox, J.F.

doi:10.1016/j.smallrumres.2010.05.010

Cited by 7 publications

(5 citation statements)

References 33 publications

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“…In addition, verapamil and cyclosporin A increased the IVM sensitivity of H. placei -resistant isolate in LMIA [ 122 ]. The investigations of verapamil toxicity are still in the early stages in livestock; for example, Pérez et al [ 128 ] reported that the co-administration of verapamil/IVM in pregnant sheep increases the bioavailability of IVM not only in maternal blood but also in fetal blood which may lead to IVM toxicity. Therefore, further research is required.…”

Section: Abc Transporters As Potential Targets To Control Nematodesmentioning

confidence: 99%

Importance of ABC Transporters in the Survival of Parasitic Nematodes and the Prospect for the Development of Novel Control Strategies

2023

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ABC transporters, a family of ATP-dependent transmembrane proteins, are responsible for the active transport of a wide range of molecules across cell membranes, including drugs, toxins, and nutrients. Nematodes possess a great diversity of ABC transporters; however, only P-glycoproteins have been well-characterized compared to other classes. The ABC transport proteins have been implicated in developing resistance to various classes of anthelmintic drugs in parasitic nematodes; their role in plant and human parasitic nematodes still needs further investigation. Therefore, ABC transport proteins offer a potential opportunity to develop nematode control strategies. Multidrug resistance inhibitors are becoming more attractive for controlling nematodes due to their potential to increase drug efficacy in two ways: (i) by limiting drug efflux from nematodes, thereby increasing the amount of drug that reaches its target site, and (ii) by reducing drug excretion by host animals, thereby enhancing drug bioavailability. This article reviews the role of ABC transporters in the survival of parasitic nematodes, including the genes involved, their regulation and physiological roles, as well as recent developments in their characterization. It also discusses the association of ABC transporters with anthelmintic resistance and the possibility of targeting them with next-generation inhibitors or nutraceuticals (e.g., polyphenols) to control parasitic infections.

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Section: Abc Transporters As Potential Targets To Control Nematodesmentioning

confidence: 99%

Importance of ABC Transporters in the Survival of Parasitic Nematodes and the Prospect for the Development of Novel Control Strategies

2023

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“…The overexpression of some of these transporters has been observed in drug-resistant isolates of different nematode species compared to susceptible reference isolates (Dicker et al, 2011;Williamson et al, 2011;Sarai et al, 2013;Raza et al, 2016), suggesting a potential role for ABC transporters in anthelmintic resistance. Numerous in vitro and in vivo studies have shown that an anthelmintic/ MDRI combination therapy increases the toxicity of the anthelmintic to both drug-susceptible and -resistant isolates of different nematode species (Bartley et al, 2009;Pérez et al, 2010;Heckler et al, 2014). Recently, Raza et al (2015) reported that zosuquidar and tariquidar, members of the so-called third generation of MDRIs (Falasca and Linton, 2012) significantly increased ivermectin (IVM) toxicity to Haemonchus contortus larvae in vitro.…”

Section: Introductionmentioning

confidence: 99%

Synergism between ivermectin and the tyrosine kinase/ P -glycoprotein inhibitor crizotinib against Haemonchus contortus larvae in vitro

Raza

Kopp

Kotze

2016

Veterinary Parasitology

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2 Graphical abstract3 Highlights:-we examined interaction of P-gp inhibitor crizotinib with ivermectin in Haemonchus contortus larvae in vitro -crizotinib increased the toxicity of ivermectin towards a resistant isolate in migration assays -less synergism observed in larval development assays -assay differences suggest life-stage specific patterns of ivermectin / P-gp interaction.-study highlights potential of P-gp inhibitors to reverse ivermectin resistance AbstractAnthelmintic resistance is a major problem in parasitic nematodes of livestock worldwide. One means to counter resistance is to use synergists that specifically inhibit resistance mechanisms in order to restore the toxicity, and hence preserve the usefulness, of currently available anthelmintics. P-glycoproteins (P-gps) eliminate a wide variety of structurally unrelated xenobiotics from cells, and have been implicated in anthelmintic resistance. Crizotinib is a tyrosine kinase inhibitor under development as a cancer therapeutic.The compound also inhibits P-gps, and has been shown to reverse multidrug resistance in cancer cells. We were therefore interested in determining if the compound was able to increase the sensitivity of Haemonchus contortus larvae to ivermectin, as measured by in vitro larval development and migration assays with a drug-resistant and a -susceptible isolate. In migration assays, co-administration of crizotinib increased the toxicity of ivermectin to resistant larvae (up to 5.7-fold decrease in ivermectin IC50), and rendered the resistant larvae equally or more sensitive to ivermectin than the susceptible isolate. On the other hand, co-administration of crizotinib had no effect on ivermectin sensitivity in the 4 susceptible isolate. In development assays, significant increases in the sensitivity of both the resistant (up to 1.9-fold) and susceptible (up to 1.6-fold) larvae to ivermectin were observed , although the magnitude of the observed synergism was less than seen in migration assays, and the resistant larvae retained significant levels of ivermectin resistance. By highlighting the ability of the P-gp inhibitor crizotinib to increase the sensitivity of H. contortus larvae to ivermectin, this study provides further evidence that P-gp inhibitors are potential tools for modulating the efficacy of anthelmintics. In addition, the differences in the outcomes of the two assays, with 'resistance-breaking' effects being much more marked in migration assays, suggest that some life-stage-specific aspects may exist in the interaction of ivermectin with Pgps in the two worm isolates.

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“…Verapamil [ 16 ] is an example of a P-glycoprotein inhibitor that can increase in vivo drug concentration by inhibiting P-gp activity. Digoxin is a ubiquitous substrate of P-gp [ 17 , 18 ] that is commonly used to screen inhibitors or revulsants of P-gp.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Assessment of the Influence of Rhizoma Zingiberis on the Level of Aconitine in Rat Gut Sacs and Qualitative Analysis of the Major Influencing Components of Rhizoma Zingiberis on Aconitine Using UPLC/MS

Yang

Liu

2015

PLoS ONE

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This study attempted to clarify the material basis for the detoxification of Rhizoma Zingiberis (RZ) on aconitine, an analgesic drug, by quantitatively assessing the influence of RZ on the in vitro intestinal concentration of aconitine using an everted gut sac model and by qualitatively identifying the components in the RZ extract. To quantify aconitine in rat everted gut sacs, both an accurate processing method and a sensitive detection method were required. We developed a three-step sample processing method to protect the components from decomposition and applied ultra-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UPLC/TQMS) to quantify aconitine, glucose and digoxin. In addition, ultra-performance liquid chromatography coupled with linear ion trap mass spectrometry (UPLC/ITMS) was applied to detect the potential antidotal components in the RZ extract. Finally, the RZ extract reduced the level of aconitine in everted gut sacs, and eleven gingerols were successfully identified, which could be considered potential antidotal components for aconitine. This study demonstrated the application of two UPLC/MS methods for analyzing the material basis for the reciprocity between Chinese medicine components in everted gut sacs.

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Influence of verapamil on pharmacokinetics and transplacental transfer of ivermectin in sheep

Cited by 7 publications

References 33 publications

Importance of ABC Transporters in the Survival of Parasitic Nematodes and the Prospect for the Development of Novel Control Strategies

Importance of ABC Transporters in the Survival of Parasitic Nematodes and the Prospect for the Development of Novel Control Strategies

Synergism between ivermectin and the tyrosine kinase/ P -glycoprotein inhibitor crizotinib against Haemonchus contortus larvae in vitro

Quantitative Assessment of the Influence of Rhizoma Zingiberis on the Level of Aconitine in Rat Gut Sacs and Qualitative Analysis of the Major Influencing Components of Rhizoma Zingiberis on Aconitine Using UPLC/MS

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