Inducing effect of albendazole on rat liver drug-metabolizing enzymes and metabolite pharmacokinetics

Amri, H. Souhaili-El; Fargetton, Xavier; Benoît, Etienne; Totis, Muriel; Batt, Anne-Marie

doi:10.1016/0041-008x(88)90236-0

Cited by 61 publications

(2 citation statements)

References 38 publications

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“…ABZ is a well-known inducer of biotransformation enzymes, mainly CYP1A subfamily in rats (El Amri et al, 1988;Asteinza et al, 2000;Baliharova et al, 2003a), in human, rabbit and HepG2 cells (Rolin et al, 1989;Galtier, 1991;Galtier et al, 1997;Baliharova et al, 2003b). However, extrapolation of the data obtained in rodents and human to game or farm animals is not possible because of interspecies differences in regulation of CYPs.…”

Section: Discussionmentioning

confidence: 96%

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A single adulticide dose of albendazole induces cytochromes P4501A in mouflon (Ovis musimon) with dicrocoeliosis

Lamka¹,

Křížová²,

Cvilink³

et al. 2007

Vet. Med. - Czech

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Contact handling with wild or semi-domesticated animals requires limiting animal stress to minimum. In this respect, single administration of drug should be preferred in contact therapy of mouflon (Ovis musimon) infected by lancet fluke (Dicrocoelium dendriticum). We tested single administration of albendazole (ABZ) (30 mg/kg of body weight) in a form of oral suspension and investigated to reach anthelmintic effects and to modulate biotransformation enzymes in liver and small intestine. Two weeks after ABZ administration coprology and necropsy findings document the adulticide effect in liver. The activities of eight biotransformation enzymes and ABZ biotransformation were tested in hepatic and intestinal subcellular fractions from control and ABZ treated animals. The highest inductive effect of ABZ was detected on cytochromes P4501A (CYP1A) activities. Increased amount of CYP1A proteins was confirmed using western blotting. In hepatic and intestinal microsomes, velocity of albendazole sulfoxide (ABZSO) formation was unaffected, but a shift in ratio of individual ABZSO enantiomers was observed. The second step of ABZ biotransformation corresponding to the formation of the pharmacologically inactive albendazole sulfone, was significantly accelerated both in liver and intestine of ABZ treated animals. The increase of ABZ deactivation could facilitate the development of anthelmintic resistance in parasites. Although single ABZ dose is therapeutically effective, its potential to induce CYP1A should be taken in account for controling helmithoses.

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Section: Discussionmentioning

confidence: 96%

“…The formation of pharmacologically inactive ABZSO 2 (second step of ABZ sulfoxidation) is mainly catalysed by CYP1A (El Amri et al, 1988). A significant increase of ABZSO 2 formation was observed in hepatic as well as in intestinal microsomes from ABZ treated animals.…”

mentioning

confidence: 82%

A single adulticide dose of albendazole induces cytochromes P4501A in mouflon (Ovis musimon) with dicrocoeliosis

Lamka¹,

Křížová²,

Cvilink³

et al. 2007

Vet. Med. - Czech

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Time dependent pharmacokinetics of albendazole in human

Mirfazaelian

Rouini

Dadashzadeh

2003

Biopharm & Drug Disp

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The pharmacokinetics of the main metabolites of albendazole (albendazole sulphoxide (ABZ-SO) and albendazole sulphone (ABZ-SO2) were studied in 12 healthy human volunteers in a double blind design on the first and last days of oral administration of 800 mg albendazole daily for 15 days. No significant differences were observed in C(max), T(max) and V(d)/F of ABZ-SO, whereas the AUC, AUMC and T(1/2) of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. There were also no significant differences in the C(max), T(max), V(d)/F and T(1/2) of ABZ-SO2, whereas the AUC and AUMC of this metabolite were significantly reduced and Cl/F was significantly increased in multiple dosing. These observations suggest time dependent pharmacokinetics of albendazole (observed for ABZ-SO and ABZ-SO2), which was explained on the basis of the induction of enzymes involved in the metabolism of ABZ-SO (albendazole sulphoxide) to metabolites other than albendazole sulphone in multiple dosing.

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Species differences in the generation of the chiral sulfoxide metabolite of albendazole in sheep and rats

Delatour

Benoît

Caude³

et al. 1990

Chirality

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The prochiral anthelmintic drug albendazole was administered orally to sheep and rats. Blood samples were taken at standardized intervals during the time course of the plasma kinetics: 18 h in rats and 48 h in sheep. The enantiomeric ratio of the sulfoxide metabolite was determined by means of HPLC on a chiral stationary phase, the chiral selector of which was a N-3,5-dinitrobenzoyl derivative of (S)-tyrosine. Two enantiomers were detected in both animal species but their ratios were inverted in rat vs. sheep. The evolution of the ratio is turned from a racemate at 15 min to 60(-):40(+) at 12 h in rats, while it moved from 23(-):77(+) at 3 h to 4(-):96(+) at 36 h after administration in sheep.

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Inducing effect of albendazole on rat liver drug-metabolizing enzymes and metabolite pharmacokinetics

Cited by 61 publications

References 38 publications

A single adulticide dose of albendazole induces cytochromes P4501A in mouflon (Ovis musimon) with dicrocoeliosis

A single adulticide dose of albendazole induces cytochromes P4501A in mouflon (Ovis musimon) with dicrocoeliosis

Time dependent pharmacokinetics of albendazole in human

Species differences in the generation of the chiral sulfoxide metabolite of albendazole in sheep and rats

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