Showing papers by "Mark A. Mintun published in 1981"
TL;DR: A model for the initial steady-state dissolution rate of a monoprotic carboxylic acid was derived from Fick's second law of diffusion, and was found to predict the dissolution rates of these acids accurately as a function of the bulk solution pH.
183 citations
TL;DR: A model was developed for the flux of a solid monoprotic carboxylic acid in aqueous buffered solutions as a function of the solution pH and the physicochemical properties of the buffer, which accurately predicts the dissolution of 2-naphthoic acid.
151 citations
TL;DR: It is unlikely that the noninstantaneous ionization kinetics demonstrated for this compound play a major role in determining the dissolution rate, either in vitro or in vivo, since the average residence time in a typical aqueous diffusion layer for phenylbutazone dissolution is longer than the reaction time for its ionization.
27 citations
TL;DR: Although initial TBW could be predicted from arterial plasma concentrations of HTO during 20 minutes after injection in normally hydrated dogs, values during 60 minutes were required for accurate prediction of TBW after infusion of 4 L of fluid.
Abstract: Using computer analysis of the early plasma arterial disappearance curve of tritiated water (HTO), we sought the fewest points and earliest times needed to predict the final volume of dilution, total body water (TBW). In ten anesthetized adult female dogs weighing 19.1 +/- 0.5 kg, with bilateral ureteral ligation, 500 muC HTO were given IV. Arterial blood samples were taken until equilibrium (3 hours), when the approximate equivalent of extracellular fluid (ECF), 4,000 ml of lactated Ringer's solution, was given IV within 1 hour. The next day, in the second phase of the study, 1,000 muC of HTO were given IV and arterial blood samples were taken at intervals up to equilibrium (5 hours). TBW at 3 hours after the first HTO infusion was 63.3 +/- 1.2% body weight. Using a curve-fitting Fortran program (CFIT), the arterial plasma HTO concentrations were fitted to one or two exponentials. Although initial TBW could be predicted from arterial plasma concentrations of HTO during 20 minutes after injection in normally hydrated dogs, values during 60 minutes were required for accurate prediction of TBW after infusion of 4 L of fluid. TBW in normal and fluid-loaded animals was predicted within 2.3 +/- 0.6% of the final HTO equilibrium (r = 0.987).
1 citations
01 Jan 1981
TL;DR: In this article, a linear system approach was used to evaluate the second peak in the blood drug concentration profile after oral dosing of cimetidine using deconvolution, which is a valuable alternative to linear compartmental or physio- logical modeling.
Abstract: The pharmacokinetics of cimetidine were evaluated using a linear system analysis that was formulated specifically to resolve the second peak in the blood drug concentration profile after oral dosing. The analysis exemplifies a new approach to pharmacokinetic modeling, which appears to be a valuable alternative to linear compartmental or physio- logical modeling. The formulation of linear system analysis according to a certain interpretation of a pharmacokinetic phenomenon avoids the complexity of conventional modeling, which often obscures the signifi- cance of the kinetic parameters. The new approach should result in a more rational analysis of pharmacokinetic phenomena because the less important pharmacokinetic processes are not specifically modeled but are still accounted for in the mathematical treatment. The bioavailability of cimetidine calculated by deconvolution agrees with previous findings. The model proposed to describe the second peak after oral absorption appears to agree well with the data and the hepatic recycling reported for cimetidine. Keyphrases 0 Linear system approach-evaluation of pharmacoki- netics of cimetidine o Pharmacokinetics-cimetidine, evaluation by linear system approach 0 Cimetidine-evaluation of pharmacokinetics by linear system approach