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Biomedical subjects

S F Chang

Publications and source records attributed to S F Chang.

At least 109 records · Page 6Linked to original sources
PubMed1988

Pharmacokinetics of flecainide in patients with cirrhosis of the liver.

The pharmacokinetics of flecainide were studied in six patients with cirrhosis of the liver and in six healthy subjects after a single 2 mg/kg intravenous dose. Hepatic biotransformation capability before flecainide dosing was assessed by antipyrine challenge. The mean plasma antipyrine t1/2 for patients (42.2 hours) was longer (p less than 0.01) than that for subjects (11.7 hours). For control subjects, the plasma t1/2 of flecainide (9.5 hours) was shorter (p less than 0.01), plasma clearance (9.1 ml/min/kg) was faster (p less than 0.01), and volume of distribution (7.5 L/kg) was smaller (p less than 0.05) compared with corresponding values in patients. Renal clearance did not differ (p greater than 0.05) between the two groups. The mean ratio of renal clearance to plasma clearance for subjects (0.4) was smaller (p less than 0.05) than that for patients. The slower rate of flecainide elimination from plasma in patients is likely due to reduced hepatic biotransformation. In patients with cirrhosis, plasma levels of flecainide may accumulate to unacceptably high levels with usual dosage regimens.

Adult↗
PubMed1987

Intranasal drug delivery for systemic medications.

This article is designed to provide a critical literature review on the scientific advances in intra- and transnasal drug delivery for systemic medication. The article discusses the fundamentals, developmental concepts, and biomedical assessment of the transnasal administration of systemically effective drugs which are either easily inactivated when taken orally, due to the extensive hepatic first-pass elimination, or too large in molecular size to be absorbed efficiently, except by i.v. administration.

Absorption↗
PubMed1987

Urethane-acepromazine: a novel method of administering parenteral anesthesia in the rabbit.

Stable long-term anesthesia in the rabbit (greater than 8 hr) has been achieved by the administration of urethane and acepromazine. Twenty-five healthy male New Zealand white rabbits weighing 2 to 4 kg were used for this study. Two groups of animals were studied. The first group of 11 rabbits received urethane (1.0 g/kg) and acepromazine (1 mg/0.46 kg). This resulted in stable light plane anesthesia for 13.5 +/- 4.5 hr (mean + S.D.). The second group of 14 rabbits received urethane (1.3 g/kg) and acepromazine (1 mg/0.46 kg) which resulted in deep plane anesthesia for 23.0 +/- 4 hr. Heart rate and respiratory rate remained stable throughout the entire period and all animals were alert and without any observable side effects by 48 +/- 3 hr. This study indicates that the combination of urethane-acepromazine is a safe and reproducible parenteral anesthetic that may be used in studies of long duration in rabbits.

Acepromazine↗
PubMed1986

The effect of flecainide acetate, a new antiarrhythmic, on plasma digoxin levels.

The possible effect of oral flecainide acetate on steady-state digoxin levels was assessed in 15 healthy men. Each volunteer received digoxin 0.25 mg daily (8 AM) for 22 consecutive days and flecainide 200 mg bid (8 AM and 8 PM) on days 11 through 15. Plasma digoxin and flecainide levels were measured by radioimmunoassay and gas-liquid chromatography methods, respectively. Flecainide levels were within the range associated with suppression of premature ventricular contractions in patients. Mean plasma digoxin levels just before the 8 AM dose were 0.46 ng/mL on days 9 and 10 (baseline), 0.57 ng/mL (P less than .05) on day 13, and 0.49 ng/mL (not significant [NS]) on day 15. Compared with a mean six-hour postdose baseline digoxin level of 0.58 ng/mL, postdose levels were 0.62 ng/mL (NS) and 0.65 ng/mL (P less than .05) on days 13 and 15, respectively. On an average for each subject, predose and six-hour postdose digoxin levels increased by 24 +/- 35% and 13 +/- 19%, respectively, during coadministration. The changes in electrocardiographic intervals and vital signs that occurred during concomitant drug administration were not clinically significant although a slight prolongation of the PR interval was noted in some subjects. Unless plasma digoxin levels are in the upper end of the therapeutic range, changes in magnitude as observed in this study should be clinically inconsequential for most patients.

Adult↗
PubMed1986

Comparative absorption of inhaled and intramuscularly administered atropine.

The inhalation of atropine sulfate was investigated in a randomized, 4-period, rising-dose study. Atropine sulfate 2, 4, and 6 mg by inhalation, and atropine free base 1.67 mg (equivalent to 2.0 mg atropine sulfate) by intramuscular (IM) injection were given to 8 healthy, nonsmoking subjects. Serum atropine sulfate concentrations were monitored during an 8-h period by radioimmunoassay. Mean serum concentrations and area under the serum concentration-versus-time curves (AUC) increased as the inhaled dose increased. Peak concentrations (mean +/- SD) were 11.5 +/- 3.4, 16.4 +/- 6.2, and 18.0 +/- 3.1 ng/ml for the 2, 4, and 6 mg doses, and 11.7 +/- 2.5 ng/ml for the IM dose. The time to peak concentration for each dose was similar (mean, 0.8 to 1.9 h). The AUC ratio of the 2-mg inhaled and IM doses was 1.11 +/- 0.41. The observed bronchodilating, anticholinergic, and other pharmacologic effects were seen after all dose concentrations and were typical of atropine. This study showed that inhalation is an efficient way to administer atropine sulfate for systemic use.

Absorption↗
PubMed1985

High-performance liquid chromatographic method for the quantitation of a meta-O-dealkylated metabolite of flecainide acetate, a new antiarrhythmic.

A simple, sensitive and selective high-performance liquid chromatographic method has been developed to analyze meta-O-dealkylated flecainide, a major metabolite of flecainide acetate, in human biological fluids. Sample preparation is accomplished through the use of bonded-phase extraction columns and the samples are chromatographed on a reversed-phase system with fluorescence detection. An external calibration method is used for quantitation and the inter-day and intra-day precision and accuracy are good. The method has been used to determine metabolite levels in samples from healthy subjects and patients with arrhythmias or renal impairment.

Anti-Arrhythmia Agents↗
PubMed1985

Effects of salsalate (nonacetylated salicylate) and aspirin on serum prostaglandins in humans.

Prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and salicylic acid were measured in blood samples from 10 healthy men after administration of antiinflammatory doses of aspirin (3.9 g/day) or salsalate (3.0 g/day). Each medication was given for 3 days, followed by an observation period of 13 days. Plasma salicylate concentrations were slightly, but generally insignificantly, higher during aspirin dosing, although both drugs produced salicylic acid levels in the antiinflammatory range. Serum levels of PGE2 and TXB2, which reflected synthesis of cyclo-oxygenase products by platelets, were minimally affected by salsalate but profoundly suppressed by aspirin. When medication was discontinued, the effects of salsalate on serum PGE2 and TXB2 were readily reversible within 36 h, whereas the recovery from aspirin was still incomplete after 13 days of observation. These results indicate that the two orally administered salicylates have differential effects on prostaglandin synthesis in platelets and may also differ in their therapeutic and adverse effects.

Adult↗
PubMed1985

Analysis of cheese for histamine, tyramine, tryptamine, histidine, tyrosine, and tryptophane.

A method is described for determining the content of selected biologically active amines (histamine, tyramine, tryptamine) and amino acids (histidine, tyrosine, tryptophane) in cheeses by high performance liquid chromatography. The amines and amino acids were quantified by employing a counter ion-containing mobile phase and by comparing peak areas of high performance liquid chromatography charts for sample cheeses versus standard cheeses containing known amounts of added amines based on dual injections of samples and standards. Recovery of amines and amino acids varied from 87.5 to 111%. Histamine, which has been associated with food poisoning in concentrations of 185 mg/100 g in Swiss cheese and 180 to 500 mg/100 g in fish, was found in concentrations above 500 mg/100 g in Swiss cheese. The high performance liquid chromatography analytical method should be useful for screening to detect cheese samples containing toxic amounts of histamine and for research studies designed to determine the cause and effect relationships for histamine production in cheese.

Cheese↗
PubMed1985

Theophylline and dyphylline pharmacokinetics in the horse.

The pharmacokinetics of theophylline and dyphylline were determined after IV administration in horses. In a preliminary experiment, the usual human dosage (milligram per kilogram) of each drug was given to 1 horse. Results were used to calculate dosages for a cross-over study, using 6 horses for each drug. Theophylline plasma concentrations decreased triexponentially in 5 of 6 healthy horses after IV infusion of 10 mg of aminophylline/kg of body weight for 16 to 32 minutes. In the 6 horses, total body elimination rate constants were variable, and the half-life of theophylline was 9.7 to 19.3 hours. Clearance was 42.3 to 69.2 ml/hr/kg. The initial distribution phase was rapid (t1/2 approx 3.5 to 4 minutes); a 2nd distribution phase was slower (t1/2 approx 1.5 to 2 hours). Plasma concentrations of theophylline were in the assumed effective range (10 to 20 micrograms/ml) from 15 minutes until 40 minutes after time zero. The mean apparent volume of distribution was 1.02 L/kg. After bolus IV injection of dyphylline (20 mg/kg), pharmacokinetics were best described by a 2-compartment open model in 2 horses and by a 3-compartment open model in 4 horses. In the 6 horses, elimination half-life of dyphylline was 1.9 to 2.9 hours, and clearance was 200 to 320 ml/hr/kg. Plasma concentrations (approx 50 micrograms/ml) were observed at 10 minutes after injection without adverse effects. Concentrations greater than 10 micrograms/ml were observed from time zero to about 1.5 hours after injection. Theophylline induced significant increases in heart rate, but dyphylline did not affect heart rate significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminophylline↗
PubMed1984

Quantitation of flecainide acetate, a new antiarrhythmic agent, in biological fluids by gas chromatography with electron-capture detection.

A sensitive and selective gas chromatographic (GC) method for the quantitation of flecainide acetate, a new antiarrhythmic agent, was developed. The unchanged drug and internal standard were separated from biological fluids by a sequence of solvent extractions and then the drug was derivatized. The pentafluorobenzamide derivatives were chromatographed on a 3% SP-2250 glass column and detected with a nickel-63 electron-capture detector. By this method, greater than or equal to 12.5 ng of flecainide/mL can be quantitated in a 1-mL sample of plasma, saliva, or urine. The intraday precision, expressed as the RSD, at plasma levels of 12.5, 25, 50, 100, 200, 300, 400, and 600 ng/mL was 3.4, 6.2, 5.3, 6.4, 1.0, 1.6, 2.0, and 0.5%, respectively; the accuracy, expressed as relative error at these levels was -24.6, -6.9, -6.0, +0.6, +3.8, -0.3, +2.4, and -1.4%, respectively. The interday precision at these levels was 13.8, 13.0, 5.7, 7.6, 8.3, 6.1, 9.0, and 5.4%, respectively. Several other antiarrhythmic agents and one beta-blocker, which might be administered concurrently with flecainide acetate, do not interfere with the assay.

Anti-Arrhythmia Agents↗
PubMed1984

Application of a bonded-phase extraction column for rapid sample preparation of flecainide from human plasma for high-performance liquid chromatographic analysis--fluorescence or ultraviolet detection.

A simple, rapid, selective, and sensitive procedure for the monitoring of flecainide levels in human plasma is described. The drug and the internal standard--a positional isomer of flecainide--are separated from plasma by the use of a disposable extraction column packed with reversed-phase sorbent. The drug and internal standard which are selectively retained on the extraction column are eluted. An aliquot is injected onto a mu-Bondapak phenyl column and eluted with a mixture of acetonitrile and 0.06% phosphoric acid (40:60, vol/vol) at a flow rate of 2 ml/min. The eluted drug and internal standard are measured by a fluorescence detector with excitation and emission wavelengths of 300 and 370 nm, respectively. The linear range is 3-2,000 ng/ml, and the sensitivity limit is 3 ng/ml with 1 ml of plasma. The within-day coefficient of variation was 1.1-4.6% at concentrations ranging from 3 to 1,600 ng/ml. Many drugs given concomitantly with flecainide acetate do not interfere with the assay. The method compares favorably to a well-documented gas-liquid chromatographic method and is suitable for use in plasma drug level monitoring for patient management as well as in pharmacokinetic studies. Similar results were obtained using an alternate detection method (ultraviolet detection at 298 nm).

Chromatography, High Pressure Liquid↗
PubMed1983

High-performance liquid chromatographic method for the quantitation of flecainide, a new antiarrhythmic, in human plasma and urine.

A simple, selective, sensitive, and accurate high-performance liquid chromatographic method for the quantitation of flecainide in human plasma and urine is described. The method is based on initially washing the sample with hexane followed by a single extraction with hexane. The extracted drug and internal standard are chromatographed on a Zorbax TMS column with a mobile phase consisting of acetonitrile-1% acetic acid in 0.01 M pentanesulfonate (45:55, v/v). The eluent is monitored at 308 nm. This method can routinely quantitate plasma or urine flecainide concentrations as low as 22 ng/ml with a 1-ml sample and 11 ng/ml with a 2-ml sample with no interference from endogenous substances and many drugs and their metabolites. The standard curve is linear over a concentration range of 22-1746 ng/ml. The precision and accuracy of the described method are suitable for monitoring flecainide levels in therapeutic, tolerance, and pharmacokinetic studies in humans.

Anti-Arrhythmia Agents↗