Diminazene aceturate residues in the tissues of healthy, Trypanosoma congolense and Trypanosoma brucei brucei infected dogs

Onyeyili, P. A.; Anika, S. M.

doi:10.1016/0007-1935(91)90106-w

Cited by 28 publications

(29 citation statements)

References 9 publications

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“…However, due to the very large Ttom value of 277 h, it is unlikely that the delay in absorption phase results from the gall bladder, as the normal release of bile occurs in cycles of 27 h. This therefore suggests that billiary excretion via an enterohepatic circulation is not the cause of the prolonged mean residence time of the drug but rather that the drug was sequestered and released elsewhere in the body. Considering that the kidney and liver showed the highest concentration in the study by Onyeyili and Anika 16 , it is suggested that the drug distributes to these organs and is released from these tissues over time, perhaps even to nucleic acids as seen with imidocarb. Also evident from the model was the slow half-life of the release of drug from the area of binding and its subsequent re-entry into the central compartment.…”

Section: Discussionmentioning

confidence: 97%

“…According to this study the drug was both rapidly excreted and distributed. In another study, the tissue kinetics of diminazene, in dogs, followed the recommended intramuscular route of administration at a dose of 3.5 mg/kg 16 . In contrast to the 1st study 16 , no drug was detectable in the plasma as early as 48 h postadministration.…”

Section: Introductionmentioning

confidence: 99%

“…In another study, the tissue kinetics of diminazene, in dogs, followed the recommended intramuscular route of administration at a dose of 3.5 mg/kg 16 . In contrast to the 1st study 16 , no drug was detectable in the plasma as early as 48 h postadministration. The drug was, however, present in very high concentrations in the liver and kidney at 48 h with the concentration in the liver being twofold higher, and was still present in these tissues 10 days post-administration.…”

Section: Introductionmentioning

confidence: 99%

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The intravenous pharmacokinetics of diminazene in healthy dogs

Naidoo¹,

Mulders²,

Swan³

2009

J. S. Afr. Vet. Assoc.

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Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs . Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil®, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUClast), clearance (CL) and volume of distribution (Vz) were 4.65±1.95 ng/mℓ/h, 0.77±0.18 ℓ/kg/h and 2.28±0.60 ℓ/kg, respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 ± 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70±5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The intravenous pharmacokinetics of diminazene in healthy dogs

Naidoo¹,

Mulders²,

Swan³

2009

J. S. Afr. Vet. Assoc.

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“…Um aspecto interessante observado em trabalhos científicos anteriores realizados com cães infectados experimentalmente por Trypanosoma brucei brucei é que a infecção por esse protozoário retarda marcadamente a eliminação corporal do aceturato de diminazeno ) e aumenta seus níveis no encéfalo (Onyeyili & Anika 1991), o que talvez explique a predileção por afetar vasos sanguíneos apenas dessa região. Resultados semelhantes foram também obtidos com infecção experimental por T. congolense em cães .…”

Section: Discussionunclassified

Aspectos epidemiológicos, clínicos e anatomopatológicos da intoxicação por aceturato de diminazeno em cães

Flores

Pereira

Mazzantí³

et al. 2014

Pesq. Vet. Bras.

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Pesq. Vet. Bras. 34(7):667-674, julho 2014 667 RESUMO.-Os aspectos epidemiológicos, clínicos e anatomopatológicos da intoxicação espontânea por aceturato de diminazeno foram estudados em 10 cães. Em todos os casos, os cães afetados demonstraram sinais de síndrome tálamo--cortical, principalmente alteração do nível de consciência, tetraparesia, rigidez extensora e crise convulsiva. Em alguns casos, os cães acometidos apresentaram sinais de síndrome cerebelar, como tremores musculares generalizados de alta frequência e baixa amplitude, e/ou de síndrome vestibular, como ataxia, inclinação de cabeça e quedas. Esses sinais ocorreram entre 24 e 48 horas após o uso do fármaco injetável por via intramuscular e se mantiveram até a morte ou eutanásia dos cães (entre 1 e 7 dias). Tais sinais clínicos refletiam encefalomalacia hemorrágica focal simétrica, que afetava a medula oblonga, a ponte, a medular do cerebelo, o tálamo, o mesencéfalo, os pedúnculos cerebelares e os nú-cleos da base. Esse artigo: 1) descreve e discute essa forma de intoxicação medicamentosa tão pouco citada na literatura internacional e desconhecida da maior parte dos clínicos e patologistas veterinários brasileiros, 2) estabelece crité-rios clínicos e anatomopatológicos para o seu diagnóstico e, principalmente, 3) atenta para os riscos da utilização desse princípio ativo na terapêutica canina. The epidemiological, clinical, and pathological aspects of diminazene aceturate (DA) spontaneous toxicosis were evaluated in 10 dogs. All affected dogs developed signs of thalamic-cortical syndrome, characterized mainly by neurological changes in the conscience levels, tetraparesis, extensor stiffness, and seizures. In some cases there was also evidence of cerebellar syndrome, characterized by generalized muscle tremors (high-frequency and low-amplitude) and/or vestibular syndrome, characterized by or ataxia, head tilt, and falling. These clinical signs occurred between 24 and 48 hours following intramuscular administration of DA and persisted until spontaneous death or euthanasia occurred between 1 and 7 days after the onset of clinical signs. The mentioned clinical signs reflected lesions that consisted of focal symmetrical hemorrhagic encephalomalacia affecting medulla oblongata, pons, cerebellar medulla, thalamus, midbrain, cerebellar peduncles, and basal nuclei. This article (1) describes and discusses DA toxicosis in dogs, a poorly-described clinical entity that is unknown by most clinicians and pathologists in Brazil; (2) establishes the clinical and pathological criteria for the diagnosis of DA toxicosis in dogs; and (3) calls up the attention for the risks of using DA in dogs in clinical settings.

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“…Secnidazole is widely distributed in the body and crosses the blood brain barrier in sufficient quantity (Rang et al, 1996). Diminazene aceturate is limited in its distribution in the brain due to its polarity, thus, it does not accumulate in therapeutic concentration (Onyeyili and Anika, 1991). Therefore, sequestered trypanosomes in the brain are not eliminated.…”

Section: Author(s) Agree That This Article Remain Permanently Open Acmentioning

confidence: 99%

Chemotherapeutic efficacy of secnidazole-diminazene aceturate combination therapy in experimental Trypanosoma brucei brucei infection in rats

Eke¹,

Ezeh²,

Ezeudu³

et al. 2017

Afr. J. Pharm. Pharmacol.

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The chemotherapeutic efficacy of secnidazole-diminazene aceturate (SEC-DA) combination therapy was studied in rats experimentally infected with Trypanosoma brucei brucei with a view of eliminating relapse of infection. Twenty rats grouped into 4 groups (n = 5) were used for the study as follows: uninfected untreated (A), infected untreated (B), infected and treated with diminazene (DA) (3.5 mg/kg) alone intraperitoneum (IP) once (C), infected and treated with SEC (200 mg/kg, orally) + DA (3.5 mg/kg, IP) (D). Treatment started 8 days post-infection. Parasites disappeared from the blood of the SEC-DA treated rats after 3 days of treatment against 5 days for DA alone. Relapse infection occurred in DA alone, 13 days post-treatment. There was no relapse infection in the SEC-DA-treated rats up to 70 days post-treatment. Hematological profiles of the animals after treatment showed significantly (p < 0.05) higher total leucocytes, lymphocytes and neutrophil in the SEC-DA group when compared with DAtreated group. Significant (p < 0.05) increase in the hemoglobin concentration and a decrease in the alanine transaminase (ALT) activity were also observed in the SEC-DA group as compared to the DA alone treated group. It is concluded therefore that the SEC-DA combination therapy was more efficacious than DA alone.

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Diminazene aceturate residues in the tissues of healthy, Trypanosoma congolense and Trypanosoma brucei brucei infected dogs

Cited by 28 publications

References 9 publications

The intravenous pharmacokinetics of diminazene in healthy dogs

The intravenous pharmacokinetics of diminazene in healthy dogs

Aspectos epidemiológicos, clínicos e anatomopatológicos da intoxicação por aceturato de diminazeno em cães

Chemotherapeutic efficacy of secnidazole-diminazene aceturate combination therapy in experimental Trypanosoma brucei brucei infection in rats

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