Bioavailability of albendazole sulphoxide after netobimin administration in sheep: effects of fenbendazole coadministration.

Merino, Gracia; Alvarez, Ana I.; Redondo, Pedro A.; García, José Luis Sánchez; Larrodé, O.M.; Prieto, J. E.

doi:10.1053/rvsc.1998.0276

Cited by 6 publications

(3 citation statements)

References 14 publications

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“…ABZ was not detected in any plasma sample. Its extensive metabolization to ABZSO and ABZSO 2 , and the plasma profiles obtained in this study for both metabolites after oral administration to sheep are consistent with those previously published in other studies [ 11 , 14 , 21 , 41 , 42 , 43 , 44 , 45 ].…”

Section: Discussionsupporting

confidence: 91%

Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

Díez

Diez

García

et al. 2022

Animals

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The pharmacokinetic interaction between a benzimidazole (albendazole, ABZ) and a choleretic drug (menbutone, MEN) was evaluated in sheep. The plasma disposition of albendazole sulfoxide (ABZSO, active metabolite) and albendazole sulfone (ABZSO2, inactive metabolite) was investigated following an oral administration of albendazole (ABZ) (5 mg/kg) alone or with menbutone (MEN) (intramuscular, 10 mg/kg). Blood samples were collected over 3 days post-treatment, and drug plasma concentrations were measured by high performance liquid chromatography (HPLC). ABZSO was measured from 0.5 to 48 h, and ABZSO2 from 2 to 60 h. No parent drug was detected at any sampling time. Mean maximum plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC) were 12.8% and 21.5% higher for ABZSO when ABZ and MEN were administered together, which indicates a significant increase in the amount absorbed. The rate of absorption was not modified, with similar values for the time to reach Cmax (tmax) (11.5 h with ABZ + MEN and 10.7 h with ABZ treatment), although no significant differences were observed for these latter pharmacokinetic parameters. Regarding ABZSO2, Cmax, AUC and tmax values were similar after both treatments (ABZ or ABZ + MEN). The results obtained indicate that co-administration of ABZ and MEN may be an interesting and practical option to increase the efficacy of this anthelmintic.

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Section: Discussionsupporting

confidence: 91%

Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

Díez

Diez

García

et al. 2022

Animals

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“…Although other tissues such as the gastrointestinal (GI) mucosa and lung may be involved (Virkel et al, 2004a), a higher metabolic capacity and first-pass oxidation in the liver is the likely explanation for the absence of the ABZ in the systemic circulation. The pharmacokinetic profiles of ABZSO and ABZSO 2 obtained in this study were similar to data previously reported in the literature (McKellar et al, 1993;Cristofol et al, 1997;Merino et al, 1999). In the present study, the C max of ABZSO (4.1 μg/ml) was almost four times higher and reached t max (14.7 h) significantly earlier than with ABZSO 2 (C max = 1.1, t max = 23.8 h).…”

Section: Discussionsupporting

confidence: 91%

Plasma Disposition and Faecal Excretion of Netobimin Metabolites and Enantiospecific Disposition of Albendazole Sulphoxide Produced in Ewes

2006

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Netobimin (NTB) was administered orally to ewes at 20 mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment and analysed by high-performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of albendazole sulphoxide (ABZSO) enantiomers produced was also determined. Neither NTB nor albendazole (ABZ) was present and only ABZSO and albendazole sulphone (ABZSO(2)) metabolites were detected in the plasma samples. Maximum plasma concentrations (C(max)) of ABZSO (4.1 +/- 0.7 microg/ml) and ABZSO(2) (1.1 +/- 0.4 microg/ml) were detected at (t(max)) 14.7 and 23.8 h, respectively following oral administration of netobimin. The area under the curve (AUC) of ABZSO (103.8 +/- 22.8 (microg h)/ml) was significantly higher than that ABZSO(2)(26.3 +/- 10.1 (microg h)/ml) (p < 0.01). (-)-ABZSO and (+)-ABZSO enantiomers were never in racemate proportions in plasma. The AUC of (+)-ABZSO (87.8 +/- 20.3 (microg h)/ml) was almost 6 times larger than that of (-)-ABZSO (15.5 +/- 5.1 (microg h)/ml) (p < 0.001). Netobimin was not detected, and ABZ was predominant and its AUC was significantly higher than that of ABZSO and ABZSO(2), following NTB administration in faecal samples (p > 0.01). Unlike in the plasma samples, the proportions of the enantiomers of ABZSO were close to racemic and the ratio of the faecal AUC of (-)-ABZSO (172.22 +/- 57.6 (microg h)/g) and (+)-ABZSO (187.19 +/- 63.4 (microg h)/g) was 0.92. It is concluded that NTB is completely converted to ABZ by the gastrointestinal flora and absorbed ABZ is completely metabolized to its sulphoxide and sulphone metabolites by first-pass effects. The specific behaviour of the two enantiomers probably reflects different enantioselectivity of the enzymatic systems of the liver that are responsible for sulphoxidation and sulphonation of ABZ.

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“…New approaches for chemotherapy need to focus on the modulation of albendazole metabolism. One potentially useful approach is the combination of albendazole with other drugs, such as the structural analogue fenbendazole (Galtier et al 1986;Merino et al 1999) or metabolic inhibitors such as methimazole (Lanusse et al 1993) and cimetidine (Wen et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Effect of clotrimazole on microsomal metabolism and pharmacokinetics of albendazole

Merino

Molina

García

et al. 2003

Journal of Pharmacy and Pharmacology

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Albendazole is a broad spectrum anthelmintic drug widely used in human and veterinary medicine. Intestinal and hepatic albendazole metabolism leads to albendazole sulfoxide (active metabolite) and albendazole sulfone (inactive metabolite) formation. Microsomal sulfonase activity can be abolished by in-vitro interaction with clotrimazole and pharmacokinetic studies confirm this interaction. After albendazole incubation, albendazole sulfone formation was completely inhibited by 50 microM clotrimazole in intestinal incubations and a 50% inhibition was observed in hepatic incubations. The lower inhibition constant (K(i)) value observed in the intestinal incubations (9.4 +/- 1.0 microM) compared with the hepatic counterparts (23.3 +/- 15.8 microM) pointed to a greater affinity of the enzymatic systems in the intestine. Regarding the formation of albendazole sulfoxide, an inhibition close to 50% was observed in liver and intestine at 10 microM clotrimazole. The pharmacokinetic parameters obtained following the oral co-administration of albendazole sulfoxide and clotrimazole corroborated the in-vitro inhibition of albendazole sulfone formation, since the ratio of the area under the plasma concentration-time curves for the sulfoxide/sulfone (AUC(ABZSO)/AUC(ABZSO2)) was significantly higher (38.1%). In addition, the AUC and C(max) for albendazole sulfone were significantly lower. The effect of clotrimazole was also studied after prolonged treatment. Hepatic microsomal metabolism of albendazole was induced after 10 days of clotrimazole administration, with significant increases in formation of albendazole sulfoxide (40%) and sulfone (27%). These results offer further insight into the metabolism of benzimidazole drugs and highlight the difficulty involved in human therapy with these anthelmintics, since after prolonged treatment the drug interactions are affected differentially.

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Bioavailability of albendazole sulphoxide after netobimin administration in sheep: effects of fenbendazole coadministration.

Cited by 6 publications

References 14 publications

Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

Improvement of Albendazole Bioavailability with Menbutone Administration in Sheep

Plasma Disposition and Faecal Excretion of Netobimin Metabolites and Enantiospecific Disposition of Albendazole Sulphoxide Produced in Ewes

Effect of clotrimazole on microsomal metabolism and pharmacokinetics of albendazole

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