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Biomedical subjects

W L Chiou

Publications and source records attributed to W L Chiou.

At least 109 records · Page 6Linked to original sources
PubMed1980

Compartment- and model-independent linear plateau principle of drugs during a constant-rate absorption or intravenous infusion.

A simple general equation is derived to show the linear plateau principle under various conditions during or after a constant or changing rate of absorption or intravenous infusion. The time required to cause a certain fraction (ft) of the total shift or change between the two steady-state plasma concentrations is equal to the time required for the cumulative (from time zero) plasma area, AUC 0 leads to t, to reach the same fracton of AUC 0 leads to infinity assumed to be obtained after an instantaneous intravenous dosing. The role of the terminal biological half-life and the importance of the early distribution phase and its exponential half-life or lives in the plateau principle are discussed. Clinical implications and applications to multiple dosage regimens are also discussed.

Humans↗
PubMed1980

Midpoint back-extrapolation method for the rapid estimation of drugs' volume of distribution and dosage adjustment exhibiting multicompartmental characteristics.

A midpoint back-extrapolation method assuming an instantaneous drug input at the midpoint of intravenous infusion based on a linear one-compartment open model is used to estimate the apparent volume of distribution and total body clearance of drugs exhibiting multicompartmental characteristics. Error analyses indicate that the method is clinically satisfactory for drugs not showing a strong multicompartmental property. For drugs exhibiting extensive multicompartmental properties, proper corrections based on the average literature data can be made. This method requires only two to three blood samples for the estimation of clinically useful pharmacokinetic parameters.

Half-Life↗
PubMed1979

Chlorpheniramine. I. Rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine by high-performance liquid chromatography.

A method was developed for the rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine using high-performance liquid chromatography. A diethyl ether or hexane extract of the alkalinized biological samples was extracted with dilute acid which was chromatographed on a reversed-phase column using mixtures of acetonitrile and ammonium phosphate buffer as the mobile phase. Ultraviolet absorption at 254 nm was monitored for the detection and brompheniramine was employed as the internal standard for the quantitation. The effects of buffer, pH, and acetonitrile concentration in the mobile phase on the chromatographic separation were investigated. A mobile phase 20% acetonitrile in 0.0075 M phosphate buffer at a flow-rate of 2 ml/min was used for the assays of plasma and saliva samples. A similar mobile phase was used for urine samples. The drug and internal standard were eluted at retention volumes of less than 17 ml. The method can also be used to quantify two metabolites, didesmethyl- and desmethylchlorpheniramine, in the urine. The method can accurately measure chlorpheniramine levels down to 2 ng/ml in plasma or saliva using 1 ml of sample, and should be adequate for biopharmaceutical and pharmacokinetic studies. Various precautions for using the assay are discussed.

Chlorpheniramine↗
PubMed1979

Creatinine VIII: saliva levels of endogenous "true" creatinine in normal subjects.

Concentrations of endogenous "true" creatinine in saliva and serum were measured in 6 normal subjects using a specific and sensitive high-performance liquid chromatographic method. There were marked intra- and intersubject variations in saliva levels during an 11-wk study. There were also large variations in the ratios of the saliva/serum creatinine level during the one-day study for all the subjects, the average highest intrasubject variation being 481% and the range being 128% to 816%. The average ratio of saliva/serum level was 0.0999 +/- 0.097 (CV = 97%); the highest saliva level was 1.5 mg%. Lower salivary levels were probably due to the extremely low lipid solubility of creatinine resulting in a relatively slower diffusion rate than of the transport of water into the saliva. Salivary monitoring of creatinine is concluded to be of little use in indicating its concentration in plasma or serum because, unlike many other substances it does not follow the pH-partition principle for saliva/plasma distribution.

Adult↗
PubMed1979

Fluorocarbon aerosol propellants XII: Correlation of blood level of trichloromonofluoromethane to cardiovascular and respiratory responses in anesthetized dogs.

Anesthetized mongrel dogs were exposed to various concentrations of trichloromonofluoromethane. Before, during, and after the inhalation, arterial and venous blood samples were obtained for fluorocarbon analysis. After the cessation of fluorocarbon inhalation, a multiexponential decline for the blood was observed. This finding was similar to that of previous study in which the fluorocarbon was administered intravenously to unanesthetized dogs. The half-life calculated from the terminal phase was about 280 min, and the pseudodistribution equilibrium was reached about 100 min after dosing. Study of the relationship between blood fluorocarbon levels and effects on the respiration rate and arterial blood pressure indicates that the sites of these pharmacological activities are located in the blood or central compartment rather than in the peripheral compartment. The effect on the heart rate appears to be quite instantaneous after inhalation. These results might shed some light on the fast effect of the fluorocarbon propellants, which caused sudden deaths after inhalation of a large quantity.

Aerosol Propellants↗
PubMed1979

Differential thermal, solubility, and aging studies on various sources of digoxin and digitoxin powder: biopharmaceutical implications.

Unlike most organic compounds, both digoxin and digitoxin melted over a wide temperature range, with the widest range being 88 and 33 degrees for both compounds, respectively. Furthermore, the melting ranges varied markedly among several untriturated powders obtained from commercial sources and after recrystallization. Trituration produced dramatically sharper and generally lower melting temperatures. Apparent equilibrium solubility also varied considerably among different untriturated compounds. Correlation between solubility and final melting temperature was found. Results from dynamic solubility studies were used to explain the failure of trituration to enhance the apparent equilibrium solubility in certain samples. Storage at room temperature increased the melting points and decreased aqueous solubilities. Several reasons such as the presence of polymorphic and amorphous forms, crystal defects, impurities, and solvate formation were postulated to explain the findings. In a preliminary study, the in vitro dissolution rates of two commercial tablet products stored at elevated temperatures for 4-8 weeks progressively decreased. Biopharmaceutical implications and areas for further studies are discussed.

Biopharmaceutics↗
PubMed1979

Rapid compartment- and model-independent estimation of times required to attain various fractions of steady-state plasma level during multiple dosing of drugs obeying superposition principle and having various absorption or infusion kinetics.

A new general equation based only on plasma data was derived for rapid estimation of the average plasma level and the mean fraction of the steady-state plasma level attained during any multiple-dosing interval. It can be applied to any complex absorption or infusion kinetics (i.e., is not limited to zero-order or first-order kinetics) for drugs obeying linear disposition kinetic or superposition principles. The time, t, required to reach a certain mean fraction of the steady-state plasma level is equal to the time at which the plasma area from time zero to time t is equal to the same fraction of the plasma area from time zero to infinity (AUC0 leads to infinity) following a single dose. No other pharmacokinetic parameters are necessary.

Humans↗
PubMed1979

Potential pitfalls in the conventional pharmacokinetic studies: effects of the initial mixing of drug in blood and the pulmonary first-pass elimination.

The classical concept of assuming that an i.v. dose instantaneously distributes into the central or plasma compartment is reviewed, as is the potential for pulmonary first-pass effect. Based on available literature, the concept is shown to lead to serious errors in estimating pharmacokinetic parameters, particularly for drugs with high clearance.

Animals↗
PubMed1979

Chlorpheniramine. II. Effect of the first-pass metabolism on the oral bioavailability in dogs.

The pharmacokinetics of chlorpheniramine has been studied in six dogs by following the time course of plasma concentration of the drug after intravenous and oral administration of its maleate salt in solution form. After intravenous dosing the decline in chlorpheniramine plasma concentration was typically biexponential. The drug distributed rapidly and extensively to the extravascular tissues. The mean distribution phase half-life was 12.5 min, and the mean apparent volume of distribution, Vdb, was 525% of the body weight in four dogs with normal hematocrits. The mean half-life of elimination was 1.7 hr. The percent absolute availability following oral administration of the drug in the aqueous solution form was found to be dose dependent. At 100-mg dose, in six dogs, an average of 36% of the orally administered dose was found to be systemically available. At 50-mg dose, in one of the four dogs studied, no measurable plasma levels of chlorpheniramine were obtained, and the average bioavailability was only 9.4%. The average availability in four dogs at 200-mg dose was 39.4%. Even at 200-mg oral dose, the dogs did not show any signs of sedation and remained alert all through the experiment. Saturable first-pass gut and/or hepatic elimination has been postulated. The possible implications of these findings on the therapeutic effectiveness of the usual dosing regimen of chlorpheniramine in dogs are discussed.

Administration, Oral↗
PubMed1979

Plasma concentrations of propranolol and 4-hydroxypropranolol during chronic oral propranolol therapy.

1 The plasma levels of propranolol and 4-hydroxypropranolol have been measured in 17 hypertensive patients receiving chronic oral therapy with propranolol. 2 The range of plasma propranolol concentrations was from 5.3 to 300 ng/ml, and that of 4-hydroxypropranolol was from 2.1 to 36.0 ng/ml. 3 The mean (+/- s.d.) plasma concentration ratio of 4-hydroxypropranolol to propranolol was 0.130 (+/- 0.005); however, a very wide range was observed with individual values ranging from 0.057 to 0.241. 4 A statistically significant correlation was observed between the plasma concentration of 4-hydroxypropranolol and that of propranolol. 5 Propranolol and 4-hydroxypropranolol plasma concentrations were each significantly, but poorly, correlated with daily propranolol dose. 6 The clinical significance of the results has been discussed.

Adult↗