The intravenous pharmacokinetics of diminazene in healthy dogs

Abstract

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

Improved clearance of radioiodinated hypericin as a targeted anticancer agent by using a duodenal drainage catheter in rats

“…29 However, discrepancies regarding EHC do exist in the literature. Some studies clearly showed the appearance of multiple peaks, 30,31 while others reported smooth curves with a single peak. [32][33][34] But with 123 I-Hyp, we believe once re-absorbed from intestines, it is rapidly and constantly taken up by hepatocytes.…”

Clinical and therapeutic aspects of an outbreak of canine trypanosomiasis

“…DMZ: diminazene diaceturate, QS: quinapyramine sulfate, IC: Isometamidium chloride. MAMMAN, 1993;XAVIER et al, 2002;MILLER et al, 2005;NAIDOO et al, 2009;FLORES et al, 2014).…”

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

“…Nos Estados Unidos, aceturato de diminazeno tem uso proibido pelo FDA (Food and Drug Administration) (Taboada & Lobetti 2006), mas, em outros países, principalmente naqueles da África, o fármaco é ainda hoje bastante utilizado no tratamento da babesiose (Collett 2000) e da tripanossomíase (Obi et al 2013) caninas, duas dentre as causas mais comuns de morte de cães na África do Sul (Collett 2000) e Nigéria (Anene et al 2006), respectivamente. Nesses dois países, aceturato de diminazeno ainda permanece sendo o agente antiprotozoário mais comumente utilizado (Naidoo et al 2009), apesar de haver relatos de resistência por determinadas cepas de Babesia gibsoni (Hwang et al 2010) e Trypanosoma brucei brucei (Anene et al 2006). Embora a intoxicação por aceturato de diminazeno tenha sido descrita em cães desde a década de 1970, existem apenas cinco citações sobre essa toxicose na literatura internacional, a saber: 1) um resumo em anais de congresso (Boyt et al 1968), 2) um relato curto de alguns casos (Losos & Crockett 1969), 3) um trabalho científi-co experimental (Naudé et al 1970), 4) um relato de um caso (van Heerden 1981) e 5) uma descrição acerca de um caso submetido ao seminário semanal (Wednesday Slide Conference) da AFIP (Armed Forces Institute of Pathology) em 2000 (AFIP 2000).…”