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Biomedical subjects

K C Yeh

Publications and source records attributed to K C Yeh.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effects of antacids and food on absorption of famotidine.

The effect of a high potency antacid and food on the bioavailability of famotidine was studied in 17 healthy volunteers in an open randomized three-way cross-over trial. After an overnight fast, famotidine was administered to each subject as follows: 40 mg famotidine orally alone; 40 mg orally with antacid; and 40 mg orally with a standard breakfast. Coadministration of the antacid caused a small but significant reduction in the maximum plasma concentration (Cmax) of famotidine from 81.1 +/- 54.2 to 60.8 +/- 21.6 ng ml-1 (P less than 0.05) and a small decrease in the area under plasma concentration-time curve [AUC] from 443.3 +/- 249.2 to 355.0 +/- 125.1 ng ml-1 h (P greater than 0.05). However, there was only a minimal effect of food on these parameters; the Cmax and [AUC] were 81.6 +/- 29.6 ng ml-1 and 434.8 +/- 145.9 ng ml-1 h, respectively.

Antacids↗
PubMed1987

Comparative effect of famotidine and cimetidine on the pharmacokinetics of theophylline in normal volunteers.

The comparative effect of famotidine or cimetidine on theophylline disposition was determined in healthy volunteers. Cimetidine, but not famotidine, caused a reduction in the rate of elimination of theophylline. The mean total body clearance of theophylline was reduced from 57.6 ml min-1 before cimetidine to 39.5 ml min-1 during cimetidine; and the half-life was prolonged from 8.7 h before cimetidine to 12 h during cimetidine. The volume of distribution and renal excretion of theophylline were not affected by either famotidine or cimetidine.

Cimetidine↗
PubMed1985

Pharmacokinetic overview of indomethacin and sustained-release indomethacin.

Indomethacin has a moderately short half-life, usually requiring dosing twice a day or three times a day. A more convenient once or twice daily regimen is made possible with a sustained-release formulation. Following multiple-dose administration of either sustained-release indomethacin (Indocin SR) or conventional indomethacin, drug accumulation is low. Clinical studies indicate comparable safety and efficacy profiles between the two preparations. Pharmacokinetic information on both dosage forms is reviewed.

Absorption↗
PubMed1985

Assay methodology for quantification of the ester and ether glucuronide conjugates of diflunisal in human urine.

Diflunisal is a salicylate derivative with analgesic and anti-inflammatory properties. It is excreted in the urine as an ether glucuronide, a 1-O-acyl glucuronide and as unchanged drug. The 1-O-acyl glucuronide rearranges to isomeric esters of glucuronic acid under neutral to alkaline pH conditions. The development of a urine assay for the conjugates enables the elucidation of diflunisal non-linear pharmacokinetics. The assay quantitates the ether and ester glucuronides and free diflunisal in urine at 0.5-1.0 micrograms/ml. Analysis of the glucuronides does not require authentic standards.

Chromatography, High Pressure Liquid↗
PubMed1985

Dose-dependent pharmacokinetics of diflunisal in rats: dual effects of protein binding and metabolism.

The purpose of this study was to define the dual effects of saturable metabolism and saturable protein binding on the pharmacokinetics of diflunisal. Steady-state diflunisal concentration and its unbound fraction were examined in seven groups of rats to determine the relationships of infusion rate, concentration and total and unbound clearances. The total body plasma clearance decreased initially and then went up as the concentration of diflunisal increased, whereas the intrinsic clearance of unbound drug decreased with increasing concentration. The former is a consequence of saturable metabolism as well as saturable protein binding; the latter is a consequence of saturable metabolism. The fraction of unbound diflunisal increased with concentration. The biliary excretion data of ester and ether glucuronide suggested that both the ester and ether glucuronidation processes are capacity-limited, although the enzyme system for ether glucuronide has a lower Km and capacity than the system responsible for the ester glucuronidation.

Animals↗
PubMed1983

Design and pharmacokinetic application of an analog computer program (MULS) for multiple dose simulation.

MULS is a simulation program developed on an analog computer equipped with logic elements. It is designed for multiple dose simulation of commonly encountered dosing schemes: equal or unequal dosing intervals, bolus and/or constant rate drug input, with or without loading dose. Appropriate pharmacokinetic models are defined independently of dosage regimen selection. The program can be used in routine operation for visualization of drug accumulation and optimum dosage regimen. Examples of the program outputs are presented.

Computers↗
PubMed1981

Effect of antacids on the bioavailability of diflunisal in the fasting and postprandial states.

Diflunisal is long-acting salicylate derivative. We examined the effect of single concomitant doses of three antacids on diflunisal bioavailability under fasting or fed conditions (30 min after finishing a standard meal). With the use of an open, randomized, and balanced design, one 250-mg diflunisal tablet was given to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area uiven to each of 12 healthy men under six conditions: fasted, no antacid; fed, no antacid; fasted, 15 ml of aluminum hydroxide gel; fed, 15 ml of aluminum hydroxide gel; fasted, 10 ml magnesium hydroxide suspension; and fed, 15 ml of an aluminum hydroxide/magnesium hydroxide mixture. Diflunisal plasma 0- to 48-hr area under the time curve (AUC), peak plasma concentrations, and 0-to 96-hr urinary excretion were determined. Food (alone) decreased peak plasma concentrations by 16% (P less than 0.05) but did not affect AUC or urinary excretion. Under fasting conditions, aluminum hydroxide reduced AUC by 26% (P less than 0.01), peak plasma concentrations by 46% (P less than 0.01), and urinary excretion by 14% (P less than 0.05). Magenisuum hydroxide suspension (in the fasting state) increased the early plasma concentrations (by 130% at 0.5 hr and 64% at 1 hr, P less than 0.05) and increased AUC by 10% (P less than 0.05) but had no effect on urinary excretion. In the fed state neither aluminum hydroxide nor the aluminum hydroxide/magnesium hydroxide mixture had any detectable effect.

Adult↗
PubMed1979

Kinetic parameter estimation by numerical algorithms and multiple linear regression: application to pharmacokinetics.

Two numerical examples are presented to illustrate the application of the proposed method of parameter estimation in pharmacokinetics. Results for a system exemplifying first-order kinetics indicate that parameters estimated by the proposed procedure compare favorably with those estimated by a nonlinear regression method. In a simulated example characterized by Michaelis-Menten elimination kinetics, the accuracy of the estimated parameters was comparable to that expected, verifying the validity of the method. The importance of the numerical approximation algorithms was demonstrated also.

Kinetics↗
PubMed1977

Kinetic parameter estimation by numerical algorithms and multiple linear regression: theoretical.

A new method is presented for the determination of kinetic parameters based on a functional relationship among experimental data derived from the postulated model. The data, even though containing errors, are manifestations of this relationship, which should be satisfied by parameters fitted to the system. The procedure involves the use of numerical integration and/or differentiation of the data, followed by multiple linear regression. It does not require initial estimates or repetitive iteration for linear systems and can be applied to nonlinear models. The accuracy of estimated parameter depends on the goodness of the particular numerical approximation method used.

Computers↗
PubMed1976

Oil-water distribution of p-alkylpyridines.

The distribution of a homologous series of p-alkylpyridines between water and six organic solvents with varying degrees of polarity was investigated. The distribution coefficients were considered as reflections of the strength of net interactions involved in the solvents. The order was chloroform greater than octanol greater than carbon tetrachloride greater than butyl ether greater than hexadecane greater than octane. The effect of the methylene group upon the distribution coefficients differed little among the six solvents. The relative constancy was attributed to the predominance of the dispersion forces in the incremental effect.

Hydrogen-Ion Concentration↗
PubMed1976

Bioavailability assessment under quasi- and nonsteady-state conditions II: study designs.

The flexibility of bioavailability assessment at quasi-and nonsteady state is demonstrated by systematically removing experimental constraints from the study design. Mathematical expressions are derived to describe each design variation. From the resultant solutions, it is evident that the proposed method can accommodate nonuniformities in dose, dosage interval, dosage regimen, dosing cycle, sampling interval, plasma half-life, washout period, and protocol adherence. Nominal requirements for the method are linear kinetics and mean plasma concentrations estimated over time intervals beginning and ending in the log-linear region.

Biological Availability↗
PubMed1976

Interpretation of distribution coefficients of p-alkylpyridines by a modified regular solution theory.

The hypothetical hexadecane-octane distribution coefficients for the alkylpyridines were deduced from the corresponding oil-water distribution data. The values were analyzed by a modified regular solution theory. A good correlation was noted by including the Flory-Huggins entropy factor in the calculation and by considering the deviation from the geometric mean assumption.

Chemical Phenomena↗
PubMed1976

Bioavailability assessment under quasi- and nonsteady-state conditions III: Application.

The applicability of bioavailability assessment at quasi- and nonsteady state is illustrated with data from a study comparing two formulations of amitriptyline hydrochloride in humans. Relative bioavailability as a function of the observed mean plasma concentrations may be expressed in closed form, provided the affected intervals begin and end in the log-linear region. Alternatively, numerical, graphical and/or electronic computational techniques may be used to stimulate the appropriate [Cp(i)]sim, the proximity of which to [Cp(i)]obs is a function of relative bioavailability and omega. If a model can be found to fit the data adequately, it would be sufficient that only one sampled interval end in the log-linear phase.

Amitriptyline↗
PubMed1975

Bioavailability of oral dexamethasone.

Bioavailabilities of dexamethasone tablets and elixir in man were evaluated by each of 3 model-independent methods of pharmacokinetic analysis employing plasma and urinary values as determined by radioimmune assay. There were no significant differences among the results determined by the 3 methods nor between the respective availabilities of the two formulations; the latter averaged 82.6 +/- 17.7% for the elixir formulation and 78.0 +/- 12.1% for tablets.

Administration, Oral↗
PubMed1975

Bioavailability of dexamethasone. II. Dexamethasone phosphate.

Plasma levels of dexamethasone phosphate (DP) and dexamethasone free alcohol (DA) were determined by a modification of existing radioimmunoassay methodology following intravenous administration of DP in man. Areas under DA plasma profiles were a linear function of DP dosage over the 40-fold range 0.05 to 2.0 mg/kg, and, by comparison with values obtained after DA was intravenously administered, indicated an overall conversion of DP to DA of 90%. The first-order rate constant for the conversion, 4.03 hr-1, was approximately 25 times that for hydrolysis in whole blood incubated in vitro. This relationship as well as disposition kinetics suggested that the major component of DP hydrolysis occurs within highly perfused organ(s) comprising the central kinetic compartment. Eighteen subjects were studied in a crossover experiment, and no significant differences were observed in best-fit parameters for the 4 mg/ml parenteral solution of DP in current use and an experimental high potency preparation of 24 mg/ml.

Adolescent↗
PubMed1975

Bioavailability assessment under quasi- and nonsteady-state conditions. I: theoretical considerations.

A strategy was devised to permit bioavailability estimations at quasi- and nonsteady states. The proposed method retains most attributes of a steady-state comparison without being burdened by its protractiveness. The only necessary requirements are that drug disposition obeys linear kinetics and that succeeding doses are administered during the log-linear phase free from the influence of continuing absorption.

Biological Availability↗