Phase I biotransformation of albendazole in lancet fluke (Dicrocoelium dendriticum)

Cvilink, V.; Szotáková, Barbora; Křížová, Veronika; Lamka, J.; Skálová, Lenka

doi:10.1016/j.rvsc.2008.05.006

Cited by 22 publications

(23 citation statements)

References 18 publications

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“…New avenues need to be investigated in order to optimise drug use and maintain productivity. Within the host, xenobiotic compounds are metabolised by biotransformation enzyme systems, such as the flavin monooxygenase (FMO) and cytochrome P-450 (CYP 450) systems, into more polar metabolites which are easier to excrete (Cvilink et al 2009). …”

Section: Introductionmentioning

confidence: 99%

“…Oxidation, reduction or hydrolysis represent the phase I of the metabolism of drugs and the most important enzymes involved in phase I biotransformation are CYP 450 enzymes (Cvilink et al 2009). CYP 450's commonly catalyse mono-oxygenation of substrates (Cvilink et al 2009).…”

Section: Introductionmentioning

confidence: 99%

“…CYP 450's commonly catalyse mono-oxygenation of substrates (Cvilink et al 2009). The existence of CYP 450 enzyme systems has been shown in a number of helminth parasites: the trematodes Dicrocoelium dendriticum, F. hepatica and Schistosoma mansoni; the cestode, Moniezia expansa; and a number of nematodes, including Haemonchus contortus and Caenorhabditis elegans (Kerboeuf et al 1995;Kotze 1997Kotze , 1999Kotze , 2000Gotoh 1998;Alvinerie et al 2001;Solana et al 2001Solana et al , 2009Saeed et al 2002;Kotze et al 2006;Cvilink et al 2008Cvilink et al , 2009. A CYP 450-mediated pathway has been implicated in the metabolism of TCBZ in F. hepatica and probably plays a greater role in the conversion of TCBZ.SO to TCBZ.SO 2 , rather than the initial TCBZ to TCBZ.SO conversion (Alvarez et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

et al. 2010

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A study has been carried out to investigate whether the action of triclabendazole (TCBZ) is altered by using the metabolic inhibitor, ketoconazole (KTZ) to inhibit the cytochrome P450 (CYP 450) system within Fasciola hepatica. The Oberon TCBZ-resistant and Cullompton TCBZ-susceptible isolates were used for these experiments. The CYP 450 enzyme system was inhibited by a 2 h pre-incubation in KTZ (40 microM). Flukes were then incubated for a further 22 h in NCTC medium containing either KTZ; KTZ + nicotinamide adenine dinucleotide phosphate (NADPH; 1 nM); KTZ + NADPH + TCBZ (15 microg/ml); or KTZ + NADPH + triclabendazole sulphoxide (TCBZ.SO;15 microg/ml). Morphological changes resulting from drug treatment and following metabolic inhibition were assessed using scanning electron microscopy. After treatment with either TCBZ or TCBZ.SO alone, there was greater disruption to the TCBZ-susceptible isolate than the TCBZ-resistant isolate. However, co-incubation with KTZ and TCBZ/TCBZ.SO led to more severe surface changes to the TCBZ-resistant isolate than with each drug on its own, with greater swelling and blebbing of the tegument and even the loss of the apical plasma membrane in places. With the Cullompton isolate, there was limited potentiation of drug action in combination with KTZ, and only with TCBZ.SO. The results support the concept of altered drug metabolism within TCBZ-resistant isolates and indicate that this process may play a role in the development of drug resistance.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

et al. 2010

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“…Although several studies have brought unambiguous evidence in favour of enzymatic oxidation of certain xenobiotics by helminths (Alvarez et al 2005;Alvinieri et al 2001;Bártíková et al 2010;Cvilink et al 2009;Kotze Fig. 4 Comparative ex vivo uptake of SOABZ by T. spiralis larvae.…”

Section: Discussionmentioning

confidence: 99%

Enantiomerical pharmacokinetic prevalence of (+) albendazole sulphoxide in Trichinella spiralis muscle larvae

et al. 2011

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In a previous work, it was demonstrated that (+) albendazole sulphoxide (SOABZ) has higher anthelmintic activity than (-) SOABZ (Bolás-Fernández et al. J Parasitol 90:407-409, 2004). In this work, the pharmacokinetics characteristics of SOABZ and its enantiomeric forms were studied in an ex vivo model system for Trichinella spiralis isolated muscle larvae. To this end, samples of either racemic or purified SOABZ enantiomers were added to the incubation medium. Quantification of either albendazole, racemic SOABZ or its enantiomers was performed by validated HPLC methods and the effect of different SOABZ concentrations in relation to time of contact with the larvae was also analysed. Obviously, higher concentration of SOABZ in the medium leads to higher concentrations of SOABZ inside the larvae which increased in an exponential mode, thus indicating a simple diffusion process. At least 18 h of contact with the drug was required to achieve anthelmintic effects. Besides, after this time, the concentration of (+) SOABZ inside the larvae was significantly higher than that of the (-) SOABZ. From these results, it can be concluded that the higher activity found in the previous work is clearly related to the pharmacokinetic prevalence of (+) enantiomer inside the larvae.

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“…They also mentioned that, although a single ABZ dose is therapeutically effective, its potential to induce CYP1A should be taken into account for controlling helminthoses. Cvilink et al (2009) did not observe sulphoreduction of albendazole sulfoxide (ABZ.SO) in their experiments in vivo and in vitro with D. dendriticum. So it appears that reverse metabolism of ABZ.SO does not occur in lancet flukes.…”

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confidence: 86%

Strategic control of Dicrocoelium dendriticum (Digenea) egg excretion by naturally infected sheep

Manga-González¹,

Quiróz-Romero²,

González-Lanza³

et al. 2010

Vet. Med. - Czech

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ABSTRACT:The aim of this study was to determine the most appropriate months for applying albendazole (ABZ; oral suspension dose 20 mg/kg body weight) to sheep naturally infected with Dicrocoelium dendriticum and kept at pasture, in order to reduce parasite egg shedding to a minimum, mainly during the cold months and, as a result, decrease pasture contamination by viable eggs. Five animal groups (G), homogeneous as regards the number of eggs per gram (EPG) in faeces, were established. The treatment months were: G1, November and January; G2, November and February; G3, November and April; G4, January; and G5 (control), April. Ten samplings (S1-S10) were carried out every 35 to 45 days to collect faecal samples from the rectum of each animal in the five groups. The sedimentation technique and McMaster egg counting chambers were used to analyze the faecal samples. Due to the effect of albendazole (ABZ) treatments, the five groups behaved differently with regard to EPG reduction and the percentage of samples positive for D. dendriticum eggs. Using the Kruskal-Wallis test, statistically significant differences (P < 0.05) were observed between the EPG values obtained in G5 and the rest of the groups from November to May, but not from May onwards. The biggest reduction in egg excretion was obtained in G1, mainly in the cold period when elimination is highest and egg survival greatest, so G1 gave the best result, followed by G2, G4, G3 and finally G5 in descending order.

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Phase I biotransformation of albendazole in lancet fluke (Dicrocoelium dendriticum)

Cited by 22 publications

References 18 publications

Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

Enhancement of the drug susceptibility of a triclabendazole-resistant isolate of Fasciola hepatica using the metabolic inhibitor ketoconazole

Enantiomerical pharmacokinetic prevalence of (+) albendazole sulphoxide in Trichinella spiralis muscle larvae

Strategic control of Dicrocoelium dendriticum (Digenea) egg excretion by naturally infected sheep

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