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Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle
Author(s) -
LANUSSE C. E.,
TRUDEAU C.,
RANJAN S.,
PRICHARD R. K.
Publication year - 1991
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.1991.tb00810.x
Subject(s) - pharmacokinetics , zwitterion , pharmacology , oral administration , chemistry , medicine , organic chemistry , molecule
Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two‐way cross‐over design. Blood samples were taken serially over a 72‐h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO 2 ). NTB was occasionally detected in plasma between 0.5 and 1.0 h post‐treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5‐0.75 h up to 32 h post‐administration, with a C max for the zwitterion suspension of 1.21 ± 0.13 μg/ml and AUC of 18.55 ± 1.45 μg.h/ml, respectively, which were significantly higher (P < 0.01) than the C max (0.67 ± 0.12 μg/ml) and AUC (8.57 ± 0.91 μg.h/ml) for the trisamine solution. ABZSO 2 was detected in plasma between 0.75 and 48 h post‐administration. The zwitterion suspension resulted in a C max (2.91 ± 0.10 μg/ml) and AUC (51.67 ± 1.95 μg.h/ml) for ABZS0 2 , which were significantly higher (P < 0.01) than those obtained for the trisamine solution (C max = 1.67 ± 0.11 ug/ml and AUC = 22.77 ± 1.09 ug.h/ml). The ratio of AUC for ABZSO 2 /ABZSO was 2.92 ± 0.26 (zwitterion) and 2.80 ± 0.20 (trisamine). The MRT for ABZSO 2 was significantly longer (P < 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution. There was no apparent difference in t 1/2 ß , either for ABZSO (from 5.45 to 5.81 h) or ABZSO 2 (from 5.16 to 5.93 h) between the two formulations. The oral NTB formulations were not bioequivalent, with the zwitterion suspension giving approximately a twofold higher pharmacokinetic profile ( AUC) for ABZSO and ABZSO 2 than the trisamine formulation.