Failure of buparvaquone (Butalex) in the treatment of canine visceral leishmaniosis

Vexenat, Julio A.; Croft, Simon L.; Campos, José Henrique Furtado; Miles, Michael A.

doi:10.1016/s0304-4017(96)01150-8

Cited by 20 publications

(13 citation statements)

References 8 publications

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“…These authors demonstrated the low efficacy of free buparvaquone when administered at 100 mg/kg by the s.c. route (i.e., a visceral leishmaniasis murine model), which ranged from 35 to 62%, with a reduced efficacy (43%) when administered by perorally. BPQ failure was also observed in Leishmania-infected dogs treated with a drug regimen of 5 mg/kg for 12 days (22). BPQ at 20 mg/kg also failed against L. infantum-infected hamsters when administered by the intraperitoneal (i.p.)…”

Section: Discussionmentioning

confidence: 94%

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Costa-Silva

Galisteo

Lindoso

et al. 2017

Antimicrob Agents Chemother

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Visceral leishmaniasis is a fatal parasitic neglected disease affecting 1.5 million people worldwide. Based on a drug repositioning approach, the aim of this work was to investigate the in vitro immunomodulatory potential of buparvaquone (BPQ) and to establish a safe regimen to evaluate the in vivo efficacy of BPQ entrapped by negatively charged nanoliposomes (BPQ-LP) in Leishmania infantum-infected hamsters. Small-angle X-ray scattering, dynamic light scattering, and the -potential were applied in order to study the influence of BPQ on the liposome structure. Our data revealed that BPQ was located in the polar-apolar interface, snorkeling the polar region, and protected against aggregation inside the lipophilic region. The presence of BPQ also decreased the Z-average hydrodynamic diameter and increased the surface charge. Compared to intravenous and intramuscular administration, a subcutaneous route was a more effective route for BPQ-LP; at 0.4 mg/kg, BPQ-LP reduced infection in the spleen and liver by 98 and 96%, respectively. Treatment for 5 days resulted in limited efficacy, but 10 days of treatment resulted in an efficacy similar to that of a 15-day regimen. The nanoliposomal drug was highly effective, with a mean 50% effective dose of 0.25 mg/kg, reducing the parasite load in bone marrow by 80%, as detected using quantitative PCR analysis. In addition, flow cytometry studies showed that BPQ upregulated cytokines as tumor necrosis factor, monocyte chemoattractant protein 1, interleukin-10 (IL-10), and IL-6 in Leishmania-infected macrophages, eliminating the parasites via a nitric oxide-independent mechanism. This new formulation proved to be a safe and effective treatment for murine leishmaniasis that could be a useful candidate against visceral leishmaniasis.KEYWORDS Leishmania, drug delivery, liposomes, therapy T he worldwide prevalence and severity of leishmaniasis has led the World Health Organization to consider it a priority infectious disease (1). Due to the complexity of host-parasite interaction, as well as contradictory results from vaccination models, the control of infection is mainly dependent on chemotherapeutic intervention (2). There are now a number of therapies for various forms of leishmaniasis; the preferences for first-line and second-line treatment vary based on the type of disease and are often guided by regional practice. Pentavalent antimonials, such as Pentostam and Glucantime, have been used to treat leishmaniasis for the last 70 years (3). However, these drugs have multiple adverse effects and decreasing effectiveness due to the development of parasite resistance, limiting their application (4). In Brazil, pentavalent antimony is still effective for treating most infections, despite its high toxicity. Until now, Citation da Costa-Silva TA, Galisteo AJ, Jr, Lindoso JAL, Barbosa LRS, Tempone AG. 2017. Nanoliposomal buparvaquone immunomodulates Leishmania infantuminfected macrophages and is highly effective in a murine model. Antimicrob Agents

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Section: Discussionmentioning

confidence: 94%

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Costa-Silva

Galisteo

Lindoso

et al. 2017

Antimicrob Agents Chemother

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“…There are four studies investigating the efficacy of intravenous amphotericin against leishmaniasis, each with a different formulation, 47–50 with a total of 87 animals treated. Three studies evaluated the efficacy of standard amphotericin B (Fungizone®, Bristol Myers Squibb, Paris La Defence, France), diluted, respectively, in water (39 dogs), 48 Intralipid® (Pharmacia Upjohn, Guyancourt, France) (19 dogs) 49 or soybean oil (16 dogs) 52 . The fourth study by Oliva and coworkers 47 was performed with the liposomal product AmBizome® (Nextar, Paris, France), and it involved 13 dogs.…”

Section: Resultsmentioning

confidence: 99%

“…Buparvaquone. Buparvaquone, used for therapy of theileriosis, was used intramuscularly in one study in seven dogs with visceral leishmaniasis 52 at the dosage of 5 mg kg −1 every 4 days for four doses, with partial or no response in all treated animals.…”

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confidence: 99%

Treatment of canine Old World visceral leishmaniasis: a systematic review

Noli¹,

Auxilia

2005

Veterinary Dermatology

148

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Canine visceral leishmaniasis is a systemic disease caused by Leishmania infantum. The aim of this systematic review was to identify and evaluate the evidence of efficacy of interventions for treatment or prevention of canine visceral leishmaniasis, and to propose recommendations for or against their use. Forty-seven articles describing clinical trials published between 1980 and 2004 fulfilled selection criteria. The evaluation of clinical trials provided good evidence for recommending the use of meglumine antimoniate at a minimum dosage of 100 mg kg(-1) daily for at least 3-4 weeks, combined with allopurinol in order to obtain a good clinical efficacy and a reduced relapse rate. The evaluation of the articles also provided fair evidence for recommending the use of pentamidine (4 mg kg(-1) twice weekly) and aminosidine (5 mg kg(-1) twice daily) for 3-4 weeks. There was insufficient evidence for recommending the use of allopurinol alone, amphotericin B, buparvaquone, ketoconazole, enrofloxacin, and the combinations of metronidazole with spiramicyn or metronidazole with enrofloxacin. Fair evidence against the use of aminosidine at high dosages (20-80 mg kg(-1) per day) was proposed due to its side effects. Evaluation of articles on repellent measures against sand fly vectors of leishmaniasis provided good evidence for recommending deltamethrin collars and fair evidence for recommending spot-on permethrin.

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“…These findings led to the synthesis of a number of water-soluble phosphate prodrugs such as BPQ-3-phosphate and 3-phosphonooxymethyl-BPQ whose aqueous solubility is more than 3.5 mg/ml over the pH range of 3.0-7.4. These prodrugs are sufficiently stable in the gastrointestinal tract before their absorption and rapidly hydrolyzed (t 1/2 = 1.2 and 3.8 min) to the parent compound in the presence of alkaline phosphatases [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of RP-HPLC-UV method for simultaneous determination of buparvaquone, atenolol, propranolol, quinidine and verapamil: A tool for the standardization of rat in situ intestinal permeability studies

Venkatesh

Ramanathan

Mansor

et al. 2007

Journal of Pharmaceutical and Biomedical Analysis

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Failure of buparvaquone (Butalex) in the treatment of canine visceral leishmaniosis

Cited by 20 publications

References 8 publications

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Nanoliposomal Buparvaquone Immunomodulates Leishmania infantum-Infected Macrophages and Is Highly Effective in a Murine Model

Treatment of canine Old World visceral leishmaniasis: a systematic review

Development and validation of RP-HPLC-UV method for simultaneous determination of buparvaquone, atenolol, propranolol, quinidine and verapamil: A tool for the standardization of rat in situ intestinal permeability studies

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