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Biomedical subjects

C M Lai

Publications and source records attributed to C M Lai.

At least 55 records · Page 3Linked to original sources
PubMed1983

Kinetics of esmolol, an ultra-short-acting beta blocker, and of its major metabolite.

Esmolol is an ultra-short-acting beta blocker. Its kinetics was studied in eight healthy subjects after continuous intravenous infusion of 400 micrograms/kg/min over 2 hr. The concentrations of esmolol and its major metabolite, 3-[4-(2-hydroxy-3-[isopropylamino]propoxy)phenyl]propionic acid, in blood and urine were determined by gas chromatographic-mass spectrometric assay and HPLC. The distribution and elimination t1/2s of esmolol averaged 2.03 and 9.19 min. The apparent volume of distribution of esmolol averaged 3.43 l/kg and was four times the volume of the central compartment. The total clearance of esmolol averaged 285 ml/min/kg, indicating that nonhepatic routes play a predominant role in its clearance. The t1/2s of formation and elimination of the metabolite averaged 2.82 min and 3.72 hr. The ratio of the metabolite formation and elimination rate constants of the parent drug (kf/k10) averaged 0.829, suggesting that 82.9% of esmolol was converted to the metabolite (which is consistent with the urinary recovery of 71% of the dose as unconjugated metabolite). The volume of distribution and total clearance of the metabolite averaged 0.411 l/kg and 1.28 ml/min/kg. Esmolol was followed by a significant reduction of isoproterenol-induced increase in heart rate and systolic blood pressure at doses of 50, 150, and 400 micrograms/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Reconstructing NMR images from projections under inhomogeneous magnetic field and non-linear field gradients.

Both inhomogeneity in the main magnetic field and non-linearity in the gradient fields introduce errors in NMR images reconstructed from projections. It is found that the image artefacts caused by these two sources are separable. The inhomogeneous main field blurs the image while the nonlinear gradients distort the image. Firstly, blurring is removed by reconstructing the image curvilinearly in a coordinate system defined by the gradient fields. The distortions in the image are then corrected by taking an inverse coordinate transformation from the gradient-field coordinates to the spatial coordinates. Experiments performed by computer simulations are presented to demonstrate that, for the first time, accurate images can be obtained under large inhomogeneity and non-linearity in the fields. Mathematical derivations and computational techniques are also described and discussed.

Magnetic Resonance Spectroscopy↗
PubMed1982

Pharmacokinetics of hydroxyethyl starch in normal subjects.

To determine the elimination of high-molecular-weight hydroxyethyl starch (HES, Mw 450,000) in normal subjects, ten volunteers were given 500 ml 6% HES solution by intravenous infusion, and serial blood and urine samples were collected for nonglucose total carbohydrate determination. On the average, 46 and 64 per cent of the dose was excreted in the urine within two and eight days, respectively. The plasma concentration declined rapidly during the first week after infusion. The average terminal half-life was 17 days during the first 42 days, which accounted for elimination of about 90 per cent of the dose. The remainder was eliminated with a terminal half-life of 48 days determined between days 42 and 83 of the study. As expected, the infusion of HES resulted in plasma volume expansion over a 48-hour period during which time levels of nonglucose carbohydrates were above 3.5 mg/ml. HES is metabolized by alpha-amylase in the body. During the first 48 hours after infusion of HES, plasma alpha-amylase activity was significantly increased over control. Concomitantly, alpha-amylase activity in urine was also elevated but not significantly so.

Adult↗
PubMed1981

Pharmacokinetics of procainamide and N-acetylprocainamide in rats.

The pharmacokinetics of distribution and elimination of procainamide and its major metabolite, N-actylprocainamide, were studied in rats. Eight rats were selected randomly, and each received intravenously 14C-labeled procainamide hydrochloride (75 mg/kg) or 14C-labeled N-acetylprocainamide hydrochloride (86 mg/kg) according to a two-way crossover design. Serial blood samples were withdrawn for 8 hr, and cumulative urine and feces were collected for 48 hr. The plasma concentration-time relationships of procainamide and N-acetylprocainamide were characterized by one- and two-compartment open models, respectively. A pseudo-three-compartment model was necessary to characterize the time course of N-acetylprocainamide in plasma formed after administration of procainamide. The biological half-lives of procainamide and N-acetylprocainamide averaged 0.66 and 2.1 hr, respectively. The urinary excretion profiles of these drugs and the ratio of their biological half-lives in rats were similar to those in humans.

Acecainide↗
PubMed1981

Pharmacokinetics of [14C]bretylium tosylate in rats.

The pharmacokinetics of bretylium tosylate were investigated in eight male Charles River rats. Each animal received an intravenous dose (10 mg/kg) of [14C)bretylium tosylate. Serial blood samples, urine, and feces were collected for up to 72 hr. Bretylium concentrations in plasma and amounts excreted in urine and feces were determined by scintillation counting. On the average, 88 and 95% of the dose were recovered in urine and feces in 24 and 72 hr, respectively. Urinary recovery accounted for 65.6 of the dose while 29.7% was excreted in the feces. Bretylium concentrations in plasma declined triexponentially and were fitted to a three-compartment open model. Bretylium has a very high apparent volume of distribution (15 liters/kg), and its beta half-life averaged 5.5 hr. Mean values of the apparent volume of the central compartment, plasma clearance, renal clearance, and excretion rate constants of bretylium in rats were 1 liter/kg, 1.93 liters/hr/kg, 1.27 liters/hr/kg, and 1.24 hr-1, respectively. The results indicate that: (a) bretylium is strongly bound to the tissues and is eliminated by active urinary secretion and by biliary excretion in rats, and (b) there are strong similarities between the pharmacokinetics of bretylium in humans and rats and that this animal model might be suitable for interaction studies with other drugs.

Animals↗
PubMed1981

True three-dimensional image reconstruction by nuclear magnetic resonance zeugmatography.

Nuclear magnetic resonance (NMR) zeugmatographic imaging may become a safe and versatile alternative to medical imaging techniques that employ ionising and ultrasonic radiation. Most of the techniques that have been described for obtaining NMR images use single point, line, or plane scans to give a single slice, or reconstruct only a two-dimensional projection, and are relatively inefficient, complex, or difficult to scale up for use on the human body. There are a number of advantage to scanning simultaneously an approximately spherical volume to obtain a true three-dimensional image. A simple two-stage reconstruction method is described for obtaining such images efficiently with isotropic resolution, and examples are presented to demonstrate the validity and usefulness of this mode. The feasibility of high-resolution imaging on large objects is also discussed.

Diagnosis↗
PubMed1981

Bioavailability of N-acetylprocainamide from mixed diet in rats.

The purpose of this study was to determine the bioavailability of N-Acetylprocainamide (NAPA) from mixed diet in rats. Six groups of 8 male Charles River CD rats received NAPA-HCl as follows: Group I, an intravenous dose (mean 21 mg) of 14C-labelled drug. Group II, in a solution given by oral gavage with and without feed (50 mg) in a two-way crossover fashion. Groups III-VI, incorporated in diet (42-68 mg). Urine and feces were collected for 48 hours and assayed for NAPA and procainamide by a specific HPLC method. On the average, 73% of the drug was eliminated unchanged in urine. Only a small percentage (3-4%) of the intact drug was recovered in feces after intravenous or oral administration. There were no detectable levels of procainamide in urine and feces. The absolute bioavailability of NAPA from oral solution with and without feed was 87 and 90%, respectively, and from the mixed diet was 84-92%. There was no statistically significant difference between the bioavailability of NAPA from solution in fasted and fed rats or from NAPA-mixed diet, indicating that the absorption of the drug in rats was not affected by food. The relative bioavailability of the drug from mixed diet ranged from 94-103%.

Acecainide↗
PubMed1980

GLC determination of bretylium in biological fluids.

Bretylium [(o-bromobenzyl)ethyldimethylamine] is a quaternary ammonium compound used as the tosylate salt for treatment of ventricular fibrillation in humans. A sensitive assay was developed for the determination of low bretylium concentrations in plasma and urine. The internal standards were (p-bromobenzyl)ethyldimethylammonium p-toluenesulfonate and (o-methoxybenzyl)ethyldimethylammonium p-toluenesulfonate. Samples were deproteinized with acetonitrile and extracted with methylene chloride. After the evaporation of the organic phase, the residue was reacted with sodium 2,4,5-trichlorothiophenolate in methanol. This procedure yielded volatile compounds with excellent electron-capture capabilities for the GLC analysis. The assay sensitivity is 5 ng/ml. The extraction recovery of bretylium as determined by a direct radioactivity measurement was 90 and 97% for plasma and urine, respectively. The method is highly reproducible with no significant day-to-day variations. Comparisons of 60 standard plasma samples, 25 standard urine samples, and plasma samples from a dog that received [14C]bretylium showed excellent agreement between the GLC method and direct radioactivity measurement of bretylium.

Animals↗
PubMed1980

Determination of procainamide and N-acetylprocainamide in biological fluids by high-pressure liquid chromatography.

A modification of a high-pressure liquid chromatographic method for the simultaneous determination of procainamide and N-acetylprocainamide in plasma is described. The deficieicies in the specificity of the existing method were overcome by replacing the cation-exchange column and the mobile phase. The recovery and reproducibility of both procainamide and N-acetylprocainamide from human, dog, and rat plasma and urine spiked with either compound were excellent in the concentration range of 0.05--10 microgram/ml for plasma and 0.5--20 microgram/ml for urine. The comparison of this method with a specific extraction method for sets of plasma samples from human subjects and rats receiving N-acetylprocainamide and procainamide, respectively, showed no statistically significant difference.

Acecainide↗
PubMed1980

Evaluation of sustained-action chlorpheniramine-pseudoephedrine dosage form in humans.

This investigation compared the bioavailability of chlorpheniramine and pseudoephedrine from a sustained-action capsule and a combination of two reference standard tablets in 24 normal human subjects. The capsule contained 8 mg of chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride, and the tablets each contained half of the amount of the chlorpheniramine or pseudoephedrine in the capsule. Because the capsule was a combination product, a new study design had to be developed to accommodate steady-state conditions for both drugs. Each subject received the capsule (every 12 hr) and the combination of the reference tablets (every 6 hr) for 8 days according to a two-way crossover design. Serial blood and urine samples were taken during the entire study. Plasma and urine samples were assayed for chlorpheniramine and pseudoephedrine by sensitive and specific high-pressure liquid chromatographic or GLC methods. There were no significant differences in the plasma concentration profiles of chlorpheniramine and pseudoephedrine at all times, except when the capsule developed peaks or the tablets developed nadirs. The highest mean peak plasma concentrations for the capsule and the tablets were 38.7 and 32.9 ng of chlorpheniramine/,ml and 525 and 515 ng of pseudoephedrine/ml, respectively. The mean biological half-lives of chlorpheniramine and pseudoephedrine were 21.6 and 8.0 hr, respectively. The AUC and unchanged drug excreted in urine, after a single dose and at steady state, showed that the sustained-action capsule (given every 12 hr) and the reference standard tablets (given every 6 hr) were bioequivalent.

Adult↗
PubMed1980

Effect of coronary artery ligation on the pharmacokinetics of N-acetylprocainamide in dogs.

The effect of ligation of the left anterior descending and septal coronary arteries on the distribution of N-acetylprocainamide (NAPA) was studied in 13 mongrel dogs. The animals received a rapid i.v. infusion of 20 mg/kg NAPA.HCl. In 6 dogs the arteries were ligated simultaneously 10 min after administration of the drug. The other dogs received the same dose without anesthesia or surgery and served as control. Coronary ligation procedure resulted in a significantly higher initial plasma concentration of NAPA, presumably because of a significant decrease in the apparent volume of central compartment. The biologic half-life, the apparent volume of distribution and the total clearance of the drug remained unchanged in both groups of animals. The results of this study suggest that while the pharmacokinetics of elimination of NAPA remain unchanged, the distribution and the effective plasma concentration might be altered by the coronary ligation procedure under anesthesia.

Acecainide↗
PubMed1980

Bretylium tosylate intravenous admixture compatibility. I: Stability in common large-volume parenteral solutions.

The stability of bretylium tosylate in 11 common large-volume parenteral solutions was studied. Two containers of each solution, one glass and one plastic (except for mannitol and sodium bicarbonate solutions, which were available in glass only), were stored at each of the following conditions: intense light (1400-2000 foot candles), ambient room temperature with normal light, 40 degrees C, and 4 degrees C. All samples were tested at 0 and 24 hours; some samples were also tested at 48 hours and 7 days. Testing included measurement for optical density at 4000 and 600 nm, pH level, and bretylium content as determined by HPLC. The admixtures remained clear and colorless, except that mannitol precipitated out of mannitol solutions stored at 4 degrees C. No appreciable changes in pH were observed. HPLC assays showed no significant changes in bretylium tosylate concentrations. Bretylium tosylate is compatible with each of the 11 common intravenous solutions chosen for investigation under the storage conditions studied. Admixtures with mannitol should not be refrigerated, because mannitol crystallizes from solution at refrigerator temperatures.

Bretylium Compounds↗
PubMed1979

Urinary excretion of chlorpheniramine and pseudoephedrine in humans.

A specific high-pressure liquid chromatographic method for the determination of chlorpheniramine and pseudoephedrine in urine was developed and applied in a urinary excretion study of normal healthy subjects who received a sustained-release dosage form contianing 8 mgof chlorpheniramine maleate and 120 mg of pseudoephedrine hydrochloride. Five subjects received one dose on Day 1, followed by multiple dosing every 12 hr for 7 days without ammonium chloride administration. Four subjects received one dose of the sustained-release dosage form together with ammonium chloride. Urine samples were collected during the 1st day and at steady state. The method is specific and simultaneously determines choorpheniramine, two metabolites (mono- and di-desmethylchlorpheniramine), pseudoephedrine, and norpseudoephedrine. The assay recovery was less than 97% (0.06-3 microgram/ml) for chlorpheniramine maleate and less than 98% (1.5-75 microgram/ml) for pseudoephedrine hydrochloride. Excretion of chlorpheniramine and its two metabolites in urine was enhanced after ammonium chloride administration. At steady state, a change in urine pH from 5.69 to 6.46 resulted in more than a 25% decrease in chlorpheniramine and monodesmethylchlorpheniramine excretion. In spite of expected changes in its biological half-life, the overall amount of unchanged pseudoephedrine excreted in urine was not affected by urine pH, presumably because it is primarily excreted in urine as intact drug.

Chlorpheniramine↗