On the assessment of the relative magnitude of rate constants in the linear open one-compartment model.
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Body Fluid Compartments↗
Biomedical subjects
C Reppas
Publications and source records attributed to C Reppas.
Viscosity modulates blood glucose response to nutrient solutions in dogs.
The relationship between postprandial blood glucose levels and meal viscosity was studied by adding various combinations of hydroxypropylmethylcellulose to glucose solutions and administering them to female mongrel dogs. Glucose was administered as 5% or 20% solutions in water. Hydroxypropyl-methylcellulose was dissolved in the glucose solutions to yield low (5000 cP measured at 37 degrees C and 1 s-1), medium (15,000 cP) or high (30,000 cP) viscosities. High viscosity hydroxypropylmethylcellulose significantly reduced the maximum blood glucose concentration, Cmax, by 60% (5% glucose meal) and 40% (20% glucose meal) while reducing the area under the blood level vs. time curve (AUC0-3 h) by 40-50%. Medium viscosity hydroxypropylmethylcellulose reduced the Cmax at both glucose levels, but reduced the AUC only for the 5% glucose meal. Low viscosity HPMC lowered the Cmax only after the 5% glucose meal, and had no significant effect on the AUC at either glucose level. The average time to reach maximum concentration, Tmax, was prolonged two- to three-fold at all viscosity levels for the 5% glucose solutions, but was not affected when 20% glucose solutions were administered. It was concluded that hydroxypropylmethylcellulose can effectively retard the absorption of glucose from the gastrointestinal tract, and that the extent of this effect is related to the viscosity of the solution administered.
Animal Nutritional Physiological Phenomena↗
Bioavailability study of a freeze-dried sodium phenytoin-milk formulation.
The problematic bioavailability of phenytoin's (5,5-diphenylhydantoin) oral formulations serves as a stimulus for examining new formulations and/or administration conditions that may provide more predictable absorption. Attempts to achieve more consistent peroral phenytoin bioavailability from conventional solid dosage forms include changes of binder and crystal size, use of salt form, and inclusion of the drug in cyclodextrins. In addition, various factors which may affect the environment and/or the physiology of the upper gastrointestinal tract can profoundly affect the absorption of phenytoin. Among other approaches, the use of drug-milk freeze-dried formulations has been proposed to overcome problems associated with dissolution-limited bioavailability. The effect has been attributed to the formation of an amorphous precipitate during the drying process which facilitates the re-dissolution of the drug during the regeneration of the milk solution. In this work, we report comparative bioavailability studies utilizing a freeze-dried sodium phenytoin-milk formulation and a capsule formulation administered with either water or milk. In addition, the interaction of the drug with milk components was evaluated in vitro through binding and solubility studies.
Administration, Oral↗
Binding of drugs in milk: the role of casein in milk protein binding--comments on the paper by Stebler and Guentert.
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Animals↗
Unusual solubility behaviour of cyclosporin A in aqueous media.
The solubility of cyclosporin A was determined in water and in Sorensen buffers at pH 1.2 and 6.6 at temperatures ranging from 5 to 37 degrees C. No differences in solubility behaviour were observed among the three aqueous media. Solubility was found to be inversely proportional to the temperature in each medium, indicating that the heat of solution was exothermic in each case.
Cyclosporins↗
Effect of hydroxypropylmethylcellulose on gastrointestinal transit and luminal viscosity in dogs.
The effects of hydroxypropylmethylcellulose on upper gastrointestinal transit, viscosity, and water flux were studied in six dogs fistulated at the proximal duodenum and/or mid-jejunum. Combinations of different grades of hydroxypropylmethylcellulose were prepared as 2% or 3.3% solutions to yield input viscosities of low (approximately 5000 cp at 37 degrees C and 1 s-1), medium (15,000 cp), or high (30,000 cp) viscosity. Hydroxypropylmethylcellulose modified intralumenal viscosity, with a linear relationship existing between input and lumenal viscosity. With regard to transit, the lag time before the onset of chyme recovery increased linearly as a function of luminal viscosity. There was also a pronounced decrease in the first-order emptying rate constant as lumenal viscosity increased from water to low-viscosity hydroxypropylmethylcellulose, but as viscosity was further increased there was little additional change. These results indicate that water-soluble fibers can exert a significant influence on both the lumenal viscosity and the transit profile in the upper gastrointestinal tract.
Animals↗
Estimate of volume/flow ratio of gastrointestinal (GI) fluids in humans using pharmacokinetic data.
Based on the mixing tank and tube models for drug absorption, the apparent absorption rate constant is shown to be related to the fraction of dose absorbed as a function of the volume/flow ratio of GI fluids. This analysis applies to drugs that are absorbed according to first-order kinetics, without limitation by dissolution rate, lumenal decomposition, or first-pass metabolism. Analysis of pharmacokinetic data of drugs that fit these criteria and are absorbed to varying extents enabled the estimation of the volume/flow ratio of GI fluids in humans; it was found to be 1.6 +/- 0.3 (SE) hr using a mixing tank model and 0.32 +/- 0.05 hr using a tube model. These findings are discussed with respect to volume and flow parameters used in the design of various types of drug absorption studies.
Animals↗
High viscosity hydroxypropylmethylcellulose reduces postprandial blood glucose concentrations in NIDDM patients.
The ability of high viscosity hydroxypropylmethylcellulose (HPMC) to reduce postprandial glucose concentrations was assessed in patients with non-insulin-dependent diabetes (NIDDM) and healthy volunteers. The study design consisted of a two-way crossover, single-dose administration of 10 g prehydrated high viscosity HPMC, or placebo, with a standard carbohydrate-rich meal. In patients with NIDDM, HPMC reduced blood glucose concentrations at the 60-, 75-, 90-, 120- and 150-min sampling intervals, with an average reduction in the maximum postprandial blood glucose concentration, Cmax, of 24% (P < 0.05). The time at which the maximum concentration was reached, Tmax, remained unchanged. The area under the blood concentration versus time plot, AUC0-6h, was reduced by an average of 15% (P < 0.05). The blood concentration profile of insulin followed that of glucose. Concentrations were significantly lower than in the placebo phase only at the 120-min sampling time, while pharmacokinetic parameters (Cmax, Tmax and AUC0-6h) were unchanged. These results suggest that alterations in the blood glucose profile are mediated by luminal events rather than by changes in hormonal response. In contrast to the NIDDM patients, neither the pharmacokinetic parameters nor the blood glucose concentrations at specific sampling times were significantly affected by the co-administration of HPMC in healthy volunteers. Overall, the results of this study suggest that HPMC may be a useful adjunct in the management of NIDDM.
Adult↗