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Pharmacokinetics of propylthio-benzimidazole anthelmintics : modulation of liver biotransformation in sheep and cattleLanusse, Carlos Edmundo January 1991 (has links)
The aim of this research was to determine the influence of route of administration, drug formulation and modified-liver metabolism on the pharmacokinetic and metabolic patterns of benzimidazole anthelmintics in ruminants. Both route of administration and formulation dramatically affected the bioconversion of netobimin (NTB) pro-drug, N-methoxycarbonyl-N$ sp prime$-(2-nitro-5-propylphenylthio)-${ rm N} sp{ prime prime}$-(2-ethyl sulphonic acid) guanidine, and the bioavailability and disposition kinetics of its active albendazole (ABZ) metabolites in both sheep and cattle. The efficacy of NTB conversion by the gastrointestinal (GI) microflora, was markedly lower after subcutaneous (SC) administration of NTB pro-drug compared with enteral administrations in both species. Although trisamine and zwitterion formulations of NTB were bioequivalent after SC treatment, the zwitterion suspension was two-fold more bioavailable in terms of ABZ metabolites, after oral administration to cattle. ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO$ sb2$), the main metabolites found in plasma, were reversibly exchanged between plasma and GI compartments and concentrated in the abomasum. ABZ, ABZSO and ABZSO$ sb2$ were detected in the GI tract for 72 h post-NTB administration to cattle. In vitro, ABZ was oxidized into ABZSO and ABZSO$ sb2$ by liver microsomes and ruminal and ileal fluids. However, only ABZSO was reduced (back to ABZ) by these GI fluids. The rate of ABZ sulphoxidation by liver microsomes was significantly lower in cattle compared to sheep. However, while the oxidizing activity was greater in GI fluids of cattle, the reducing activity was prevalent in those of sheep. This was consistent with the higher ABZSO$ sb2$/ABZSO ratio and the markedly faster disposition of both metabolites in cattle compared to sheep. The co-administration of NTB with different oxidation-impairing compounds, largely methimazole (MTZ), in both species, resulted in an increased bioavailability and/o
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Pharmacokinetics of propylthio-benzimidazole anthelmintics : modulation of liver biotransformation in sheep and cattleLanusse, Carlos Edmundo January 1991 (has links)
No description available.
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Pharmacokinetic analysis of antimicrobials and an anthelmintic agent in alpacas and llamas with theoretical applicationsWattananat, Triporn 01 December 2003 (has links)
The pharmacokinetics of two antimicrobials were investigated in alpacas. Six
healthy alpacas were each administered a single dose of 10 mg/kg of oxytetracycline by IV
injection and IM injection. In addition, a single dose of 20 mg/kg of florfenicol by IV
administration was given to alpacas in a separate study. The pharmacokinetic parameters
of oxytetracycline and florfenicol in alpacas were compared to the results previously
obtained in llamas. There were significant differences between llamas and alpacas in
several of oxytetracycline pharmacokinetic parameters but there were no significant
differences in all of florfenicol pharmacokinetic parameters in these two animals. It can be
concluded that llamas and alpacas have different oxytetracycline disposition kinetics while
they have similar disposition kinetics of florfenicol.
The pharmacokinetics of clorsulon, a narrow-spectrum anthelmintic agent, was
investigated in llamas following oral administration at a single dose of 14 mg/kg. The
plasma levels of clorsulon produced by this dose was lower than the values reported in the
clorsulon pharmacokinetic studies carried out in sheep and goats following oral
administration at a single dose of 7 mg/kg This suggests the entire dose of clorsulon is not
absorbed in llamas.
Since the differential equations describing one-compartment system with first-order
input and two-compartment system after IV administration with nonlinear
elimination kinetics cannot be solved, there is no mathematical expression for the AUC for
drugs following these models. The AUC values calculated from the proposed preliminary
AUC equations for drugs following these models were compared to the AUC calculated
using the trapezoidal rule method based on computer-generated data using the fourth-order
Runge-Kutta method. Except for a few exceptions, the predicted AUC from the proposed
equations matched the values calculated from the theoretically generated data. / Graduation date: 2004
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