Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle
作者:
C. E. LANUSSE,
C. TRUDEAU,
S. RANJAN,
R. K. PRICHARD,
期刊:
Journal of Veterinary Pharmacology and Therapeutics
(WILEY Available online 1991)
卷期:
Volume 14,
issue 1
页码: 101-108
ISSN:0140-7783
年代: 1991
DOI:10.1111/j.1365-2885.1991.tb00810.x
出版商: Blackwell Publishing Ltd
数据来源: WILEY
摘要:
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 (ABZSO2). 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 Cmaxfor the zwitterion suspension of 1.21 ± 0.13 μg/ml andAUCof 18.55 ± 1.45 μg.h/ml, respectively, which were significantly higher (P<0.01) than the Cmax(0.67 ± 0.12 μg/ml) andAUC(8.57 ± 0.91 μg.h/ml) for the trisamine solution. ABZSO2was detected in plasma between 0.75 and 48 h post‐administration. The zwitterion suspension resulted in a Cmax(2.91 ± 0.10 μg/ml) andAUC(51.67 ± 1.95 μg.h/ml) for ABZS02, which were significantly higher (P<0.01) than those obtained for the trisamine solution (Cmax= 1.67 ± 0.11 ug/ml andAUC= 22.77 ± 1.09 ug.h/ml). The ratio ofAUCfor ABZSO2/ABZSO was 2.92 ± 0.26 (zwitterion) and 2.80 ± 0.20 (trisamine). The MRT for ABZSO2was significantly longer (P<0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution. There was no apparent difference in t1/2 ß, either for ABZSO (from 5.45 to 5.81 h) or ABZSO2(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 ABZSO2
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