PHARMACOKINETIC PROFILES OF NETOBIMIN METABOLITES AFTER ORAL-ADMINISTRATION OF ZWITTERION AND TRISAMINE FORMULATIONS OF NETOBIMIN TO CATTLE

Pharmacokinetic profiles of the major metabolites of netobimin were investigated in claves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and triasamine 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 (ABZO2). 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 mu-g/ml and AUC of 18.55 +/- 1.45-mu-g.h/ml, respectively, which were significantly higher (P < 0.01) than the C(max) (0.67 +/- 0.12-mu-g/ml) and AUC (8.57 +/- 0.91 mu-g.h/ml) for the trisamine solution. ABZSO2 was detected in plasma between 0.75 and 48 h post-administration. The zwitterion suspension resulted in a C(max) (2.91 +/- 0.10-mu-g/ml) and AUC (51.67 +/- 1.95-mu-g.h/ml) for ABZSO2, which were significantly higher (P < 0.01) than those obtained for the trisamine solution (C(max) = 1.67 +/- 0.11-mu-g/ml and AUC = 22.77 +/- 1.09-mu-g/ml). The ratio of AUC for ABZSO2/ABZSO was 2.92 +/- 0.26 (zwitterion) and 2.80 +/- 0.20 (trisamine). The MRT for ABZSO2 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 t1/2-beta 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 than the trisamine formulation.