Showing papers by "Gordon L. Amidon published in 1974"
TL;DR: The correlations show that branching, cyclization, and positional isomerism can be accounted for without introducing additional terms.
131 citations
TL;DR: The pharmacokinetic parameters were little affected by multiple dosing in normal subjects, but there was some evidence of enzyme induction in uremic patients after single and multiple intramuscular doses.
Abstract: The pharmacokinetics of the 7-amino-cephalosporanic acid derivative, cefazolin, has been studied in normal subjects and in uremic patients after single and multiple intramuscular doses. In most cases serum concentration and cumulative urinary excretion data were successfully fitted to equations appropriate to the pharmacokinetic one-compartment open madel with first-order absorption and elimination. In normal subjects cefazolin gave maximum serum concentrations of 30 to 50 fLg per milliliter 1 hour after a single 500 mg injection with a serum half-life of about 2 hours. Higher serum levels were obtained after identical doses to uremic subjects, and serum half-lives increased with decreasing renal function. The apparent distribution volume of cefazolin was slightly greater in uremic subjects and was proportional to the decrease in serum protein binding. Urine concentrations were higher in normal than in uremic subjects but were consistently above the minimum inhibitory concentrations (MIG) for most organisms in both groups. Pharmacokinetic parameters were little affected by multiple dosing in normal subjects, but there was some evidence of enzyme induction. Good linear correlations were obtained between the elimination rate constant, serum and renal clearance, and creatinine clearance, and also between the logarithms of the amount of drug eliminated unchanged and creatinine clearance. It is proposed that the observed relationships may be used for adjustment of dosage regimens in cases of renal failure.
39 citations
TL;DR: The proposed role of the buried aspartate group in activating the reactive serine oxygen in the serine proteinase enzymes is proposed with the proposed role in the CNDO/2 MO SCF method for canonical form stabilities and proton potential energy curves.
24 citations
TL;DR: Results suggest that for planar complexing systems in solution, both the solvent term and the absolute interaction energy term will usually be maximized when maximum overlapping of area occurs.
3 citations
TL;DR: The results indicate that the contribution of the nonpolar solvent carbon tetrachloride to the overall complex strength is significant and perhaps greater than the absolute interaction energy of the substrate and ligand.
2 citations
TL;DR: The structure of the methyl trans-cinnamate complexes with the theophylline and theobromine anions is calculated theoretically by maximizing the binding energy of the two interacting molecules.