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Biomedical subjects

N F Ho

Publications and source records attributed to N F Ho.

At least 73 records · Page 4Linked to original sources
PubMed1979

Effect of pH on the stability of heparin in 5% dextrose solutions.

The effect of pH and time on the stability of heparin sodium in dextrose 5% in water (D5W) injection and in dextrose 5% in 0.45% sodium chloride injection was studied. Admixtures of heparin sodium 5,000 units/250 ml were tested after 0, 10, 20 and 30 minutes and 1, 2, 6, 12 and 24 hours of storage at room temperature. The pH of the carrier solutions was adjusted to 2, 4 or 9 prior to adding the heparin sodium. Heparin activity was measured using a thrombin clotting time assay. Samples were tested for pH changes at the same times. No substantial changes in heparin activity over the 24-hour period occurred with any of the pH-adjusted solutions. The pH of the heparin-D5W admixtures remained constant over time. The two carrier solutions, over a pH range of 2 to 9, appear to be suitable vehicles for heparin sodium.

Biological Assay↗
PubMed1978

Kinetics of drug transport and concurrent metabolism in human cell cultures I: theory.

A method for evaluating the passive permeability and single-step metabolism of drugs in suspension cultures of mammalian cells was formulated assuming linear kinetics. It was assumed that the metabolizing enzymes are driven by endogenous substrates present in steady-state quantities. The presence of the drug in radiolabeled tracer quantities was assumed to cause only a small perturbation from the endogenous steady-state operating point. The time course solutions for the drug and its metabolite are given in terms of macroscopic constants, and their physical interpretations are given in terms of metabolic and transport parameters.

Biological Transport↗
PubMed1977

Systems approach to vaginal delivery of drugs IV: methodology for determination of membrane surface pH.

A physical model including a diffusional layer in series with the membrane was developed for studying the possible differences between the pH at the membrane surface and that in the bulk solution. Both the membrane-secreted substances (acids and bases) and buffer constituents in the bulk solutions are assumed to contribute to the surface pH. Equations derived for this situation, together with experimental determinations of the acidic dissociation constant of the secreted material, the total secretion flux, the flux of total secreted acidic species, and the diffusion layer thickness, allow estimates to be made of the pH at the membrane surface. With the rabbit vagina, the membrane surface pH was close to that of the bulk solution in most cases. These results were supported by the fact that the absorption of 1-alkanoic acids in pH 2.2 phosphate buffers was relatively constant over the buffer concentration range of 0.003-0.1 M phosphate.

Absorption↗
PubMed1977

Systems approach to vaginal delivery of drugs V: in situ vaginal absorption of 1-alkanoic acids.

The vaginal absorption of a homologous series of ionizable compounds, the 1-alkanoic acids, was studied using a perfusion method with a rib-cage cell surgically implanted in the rabbit vagina. The absorption rates of these compounds followed first-order kinetics. The physical model previously used for the 1-alkanols, but accounting for the pKa and pH effects in the present case was employed in the analysis of the carboxylic acid data. The aqueous diffusion layer thickness was 0.031 cm. The permeability coefficient for the lipoidal pathway increased 3.5-fold per methylene group. Both values agree reasonably well with those obtained in the alcohol study.

Absorption↗
PubMed1977

Skin as an active metabolizing barrier I: Theoretical analysis of topical bioavailability.

A model and explicit equations were developed to be used in the experimental design and data evaluation of situations where simultaneous metabolism and transport of drugs occur in the skin. By treating the skin as a two-ply laminate composed of the stratum corneum and the viable epidermis, which contains most of the catabolic enzymes that might render a drug inactive by metabolism, equations were developed permitting the in vitro assessment of factors that may affect topical bioavailability in vivo. Two situations were investigated. In the first, the drug was placed on the dermis side of the diffusion cell and did not penerate the stratum corneum. In the second, the drug, placed on the epidermis side, penetrated the stratum corneum and then passed through the metabolizing epidermis. Expressions for determining the metabolic rate constant from experimental data along with concentration profiles and flux expressions are given both for the drug and its metabolite.

Administration, Topical↗
PubMed1976

Systems approach to vaginal delivery of drugs II: In situ vaginal absorption of unbranched aliphatic alcohols.

The absorption of unbranched aliphatic alcohols in the rabbit vagina was studied using a perfusion method, and the absorption rates were found to be first order with respect to the drug concentration in the vagina from methanol to octanol. A physical model involving an aqueous diffusion layer in series with a membrane consisting of aqueous pores and lipoidal pathways was used for analyzing the data. The physically based parameters in the model were determined. An effective diffusion layer thickness ("unstirred layer") of around 0.035 cm was found. The increase in the permeability coefficient for the lipoidal pathway per methylene group was around 2.5 for this homologous series.

Absorption↗
PubMed1976

Systems approach to vaginal delivery of drugs III: Simulation studies interfacing steroid release from silicone matrix and vaginal absorption in rabbits.

A composite physical model involving the simultaneous receding boundary release of drug from a drug suspension-silicone polymer matrix system, diffusion across the aqueous layer, and passive transport across the vaginal membrane consisting of parallel lipoidal and aqueous pore pathways is described. Simulation studies with progesterone and hydrocortisone illustrate matrix release-limiting, membrane absorption, and aqueous diffusion layer-limiting cases when the cylindrical silicone delivery device is interfaced with the vaginal membrane of the rabbit.

Cell Membrane↗
PubMed1975

Systems approach to vaginal delivery of drugs I: development of in situ vaginal drug absorption procedure.

In the framework of the development of drug delivery systems for locally administered contraceptive drugs, a reliable method that can afford quantitative evaluation of drug absorption behavior was explored using the rabit doe. A system was constructed based upon perfusing the drug solution in the vaginal tract. For this purpose, a "rib-cage" type cell was constructed and surgically implanted in the rabbit prior to an experiment. The primary purpose of the present paper is to evaluate the method, including the surgical operation and the perfusion system. The absorption experiments were carried out using n-butanol-1minus 14C as the model solute to survey the reproducibility of the absorption behavior. Experiments were conducted with a number of rabbits on several successive days to determine the day-to-day and animal-to-animal variations. The drug disappearance in the reservoir followed first-order kinetics from which the apparent permeability coefficient was calculated. The results indicated that a set of experiments may be carried out on a single animal and that the method generally affords rather high precision.

Absorption↗
PubMed1975

Systems approach to study of solute transport across membranes using suspension cultures of mammalian cells III: steady-state diffusion models.

General physical models are derived for the diffusional transport of drugs across membranes of mammalian cells in culture suspension. These models represent different sets of possible physical processes taking place during the transport of a drug molecule. Once the diffusing species reaches the cell barrier, it may gain entrance to the cell kinetically by one of the principal quasisteady-state mechanisms, all of which assume the cell membrane to be an integral part of the total barrier.

Biological Transport↗
PubMed1975

Systems approach to study of solute transport across membranes using suspension cultures of mammalian cells IV: Uptake and release kinetics of sterols.

The kinetics of uptake and release of desmosterol, cholesterol, and beta-sitosterol by Burkitt lymphoma cells at 26 degrees, pH 7.3, and isoosmotic conditions were quantitatively and mechanistically interpreted. The data are in agreement with the model involving the passive transport of the unbound sterol across the rate-determining plasma membrane, with rapid distribution within the heterogeneous cell interior. Effective permeability (P-e) and partition (K-e) coefficients of the sterols were inversely proportional to the serum concentration in the external media due to sterol-serum binding. These results are consistent with the mechanism in which only the unbound solute in the external solution participates in the membrane transport process. At all serum levels, P-e and K-e increased with increasing sterol polarity: desmosterol greater than cholesterol greater than beta-sitosterol.

Animals↗
PubMed1975

Systems approach to study of solute transport across membranes using suspension cultures of mammalian cells V: Uptake and release kinetics of cardiac glycosides by Burkitt lymphoma cells.

Mass transport studies with three cardiac glycosides in the Burkitt lymphoma cell system have provided significant examples of the factorization and quantification of the influences of serum-drug binding, membrane-drug binding, cell interior binding, and intrinsic membrane permeability upon the uptake and release kinetics of drugs in living cell systems. All of the data from the glycosides are in agreement with the general physical model involving the rapid equilibration of the solute within the cell after permeation through the rate-determining plasma membrane barrier. The transport of digitoxin was influenced by membrane and serum binding and that of digoxin was influenced by membrane binding. There was no binding of ouabain to the plasma membrane and serum. The variables in the uptake and release kinetic studies at pH 7.3 included the use of viable and heat-inactivated cells, fetal bovine serum levels, and temperature.

Burkitt Lymphoma↗