No description available.

No description available.

The steroid androstenedione has been shown to be a valuable tool for the study of selective inactivation of rat liver cytochrome P-450 isozymes. The validity of this method was investigated using microsomes, purified cytochromes P-450, cytochrome P-450 antibodies, and the mechanism-based inactivator chloramphenicol. Enzyme inactivation and antibody inhibition studies show that microsomes from phenobarbital- and non-phenobarbital-treated rats are needed to accurately monitor the inactivation of the major phenobarbital-inducible P-450 isozyme (PB-B) and of the major constitutive androstenedione 16-alpha hydroxylase (UT-A). Enzyme inactivation studies showed that the antibiotic chloramphenicol caused different rates of NADPH-dependent enzyme inactivation among four androstenedione hydroxylases (16-beta > 6-beta > 16-alpha > 7-alpha). The results with twelve chloramphenicol analogs show that their selectivity as cytochrome P-450 inactivators is dependent upon at least three structural features: (1) the number of halogen atoms, (2) the presence of a para-nitro group on the phenyl ring, and (3) substitutions on the ethyl side chain.

No description available.

Bibliography: leaves 116-138.

Bibliography: leaves 162-174.

Graduation date: 1998

The disposition of four therapeutically important antimicrobial agents was studied in llamas following intravenous bolus administration. Six llamas were each given ampicillin, tobramycin, trimethoprim and enrofloxacin at a dose of 12 mg/kg, 1 mg/kg, 3 mg/kg and 5 mg/kg of body weight with a wash out period of 3 days between each treatment. Plasma concentrations of these antimicrobial agents over 12 hours following IV bolus dosing were determined by reverse phase HPLC. Dispositions of these four antimicrobial agents were described by two compartment open model with elimination from the central compartment, and also by non-compartmental methods. From compartmental analysis, the elimination rate constant, half-life, and apparent volume of distribution in the central compartment were determined. Statistical moment theory was used to determine non-compartmental pharmacokinetic parameters of mean residence time, clearance, and volume of distribution at steady-state. Based on the disposition parameters determined, a dose and dosing interval for each of the four antimicrobial agents was suggested for llamas. Steady state peak and trough plasma levels were also predicted for the drugs in this study for llamas. / Graduation date: 1994

published_or_final_version / Pharmacology and Pharmacy / Master / Master of Philosophy

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