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Biomedical subjects

S T Chiang

Publications and source records attributed to S T Chiang.

At least 55 records · Page 3Linked to original sources
PubMed1985

Experimental efficacy and pharmacokinetic properties of cefpiramide, a new cephalosporin.

The in vivo therapeutic efficacy of cefpiramide was investigated and compared with that of cefoperazone. Cefpiramide was more potent than cefoperazone against infections produced by both beta-lactamase-producing and non-beta-lactamase-producing S. aureus. The protective activity of cefpiramide against experimental infections with selected members of Enterobacteriaceae was lower than that of cefoperazone. Against carbenicillin-resistant P. aeruginosa infections, cefpiramide was as active as gentamicin and aztreonam and three times more potent than cefoperazone, cefotaxime and piperacillin. The pharmacokinetic properties of cefpiramide in mice and rats were superior to those of cefotaxime and cefoperazone. The peak serum concentrations of cefpiramide, administered subcutaneously at a dose of 50 mg/kg, were 76 micrograms/ml in mice and 174 micrograms/ml in rats and the corresponding serum half-lives of cefpiramide were 87 min and 49 min in mice and rats respectively.

Animals↗
PubMed1984

Effect of renal impairment and hemodialysis on lorazepam kinetics.

The effect of renal disease on lorazepam kinetics was assessed in three groups: six normal subjects, six patients with renal impairment, and four functionally anephric patients. Subjects received single 1.5- or 3-mg intravenous and oral doses; eight subjects (four normal and four with renal impairment) also received 0.5-mg oral doses three times a day. Lorazepam and lorazepam glucuronide were determined in plasma, urine, and feces by a highly sensitive gas chromatographic method. After single doses, t1/2 and V beta increased in patients, but Cls in the patients (about 85 ml/min) did not differ significantly from that in normals (71 ml/min). Absorption of oral dose was more than 90% and was not impaired by the disease state. Renal and fecal excretion of intact lorazepam accounted for only about 2% of the dose. The major route of drug elimination was hepatic biotransformation to lorazepam glucuronide, an inactive, nontoxic metabolite eliminated by the kidney. In both the normal and renally impaired groups, about 64% of the dose was recovered as glucuronide in urine and less than 0.4% in feces. Fecal excretion contributed very little to the overall elimination of lorazepam and its glucuronide in all groups. Only 8% of the intact drug was removed by 6-hr hemodialysis, but 40% was removed as glucuronide conjugate. Lorazepam kinetics after subchronic dosing were linear. The difference in Clo between the normal and renally impaired groups was not significant. Since the mean steady-state concentration depends on drug clearance only, and since clearance is not altered, no dosage adjustment appears necessary for patients with renal disease.

Administration, Oral↗
PubMed1984

Pharmacokinetics of guanabenz in patients with impaired liver function.

The disposition of guanabenz, a centrally acting antihypertensive agent, was compared in 10 normotensive patients (eight males and two females) with chronic hepatic disease secondary to alcohol abuse and 10 healthy male volunteers after a 16 mg oral dose. Mean plasma concentrations of guanabenz were higher in patients with liver disease than in healthy subjects at every sampling time through 72 h after drug administration (p less than 0.05). In liver disease patients, the mean oral-dose clearance (2 L/h/kg) and terminal-phase volume of distribution (20 L/kg) were lower (p less than 0.001) than the respective values of 11 L/h/kg and 71 L/kg of healthy volunteers. The mean plasma half-life of patients with liver disease (6.4 h) was not significantly longer than that of healthy subjects (4.3 h). The mean fraction of unbound drug in the plasma was higher (p less than 0.01) in patients with liver disease (12.7%) than in healthy volunteers (10.5%). As guanabenz is eliminated predominantly via hepatic biotransformation and undergoes significant presystemic elimination after oral administration, the changes in guanabenz disposition in liver disease are not unexpected. They may be explained by enhanced oral bioavailability, owing to portosystemic shunting and/or reduced intrinsic clearance, combined with decreased hepatic clearance of guanabenz in liver disease. Individual dosage titration may be required when guanabenz is used for antihypertensive therapy of patients with chronic liver disease.

Adult↗
PubMed1984

Effects of guanabenz on gastrointestinal absorption of hydrochlorothiazide.

The pharmacokinetics of guanabenz (16 mg) and hydrochlorothiazide (25 mg), administered separately and as a fixed-combination tablet (guanabenz 16 mg/hydrochlorothiazide 25 mg), were compared in a randomized three-period crossover study in 24 healthy men. Plasma concentrations were monitored for 48 h after each administration. No statistically significant differences between the two formulations were noted in mean plasma concentrations or the rate and extent of absorption of guanabenz. The relative bioavailability (Fr) of the combination tablet compared with guanabenz alone was 96%; thus the two formulations were bioequivalent with respect to guanabenz. For hydrochlorothiazide, mean plasma concentrations were similar for 3 h after administration but were higher for the combination tablet than for hydrochlorothiazide alone from 4 through 48 h (p less than 0.05). A significant increase in the extent, but not the rate, of absorption of hydrochlorothiazide was observed for the combination tablet (mean Fr, 120%), which is not considered clinically significant. We propose that this increase may have been due to increased systemic availability of hydrochlorothiazide in the presence of guanabenz, an alpha-adrenergic agonist, which may have delayed intestinal transport of hydrochlorothiazide, resulting in enhanced gastrointestinal absorption.

Adult↗
PubMed1983

A new method for measurement of respiratory resistance.

A new method for measuring the resistance of the total respiratory system is presented. The method uses a device comprising a solenoid valve, a multiperforated plate, and a pneumotachograph. The multiperforated plate serves as a constant resistor (Rk) that is used to partially occlude the airway opening, thus rapidly and briefly reducing airflow during natural expiration. If it is assumed that the driving pressure remains constant during the very short period the airway is partially occluded, the respiratory flow immediately preceding the addition of Rk (V) and the flow reduction during partial occlusion (delta V) allow calculation of the resistance of the total respiratory system. The resistance of 14 normal subjects and 18 patients with chronic obstructive pulmonary disease (COPD) was measured with this new method as well as with the body plethysmographic method: 90% of the interrupter values fell within +/- 0.6 cmH2O . l-1.s of the plethysmographic values, and all fell within +/- 0.8 cmH2O . l-1.s.

Airway Resistance↗
PubMed1982

Dose-dependent pharmacokinetics of the antihypertensive 2,3,4,4a-tetrahydro-1H-pyrazino[1,2a]quinoxalin-5-(6H)-one in dogs and rats.

A sensitive and reproducible GLC assay was developed for determining 2,3,4,4a-tetrahydro-1H-pyrazino[1,2a]quinoxalin-5(6H)-one (I) in biological fluids, utilizing the electron-capturing capability of the heptafluorobutyryl derivative. After single 2.5- and 10-mg/kg oral and intravenous doses to three dogs, plasma concentration-time data for I were fitted to a biexponential equation and pharmacokinetic parameters were calculated. A dose-dependency for certain parameters, most notably total body clearance (ClT), was indicated. The difference in ClT for the low and high dose was statistically significant. After single 5-, 25-, and 50-mg/kg intragastric doses were given to rats, the decline in plasma concentrations of I with time followed a monoexponential equation. As with dogs, there was a disproportionate change in kinetic parameters with increasing dose for rats. While simple Michaelis-Menten kinetics were not evident, nonlinearity in biotransformation (intrinsic clearance) appeared to be the cause for the dose-dependent pharmacokinetics.

Administration, Oral↗
PubMed1982

Oxaprozin disposition in renal disease.

Effects of renal disease on the disposition kinetics of oxaprozin, a nonsteroidal antiinflammatory analgesic, were assessed in 15 subjects who were normal, renally impaired, or who had been undergoing hemodialysis. Oral dose clearance (Cloral), volume of distribution at steady-state (V88d), and elimination half-life (t 1/2) did not substantially differ among the three groups. Mean fraction unbound oxaprozin in plasma (fup) increased from 0.08% in the normal group to 0.18% and 0.28% in the two azotemic groups. Consequently, unbound drug kinetic parameters, including intrinsic clearance (Clint) and V88du of unbound drug were reduced from 2.9 l/hr/kg and 193 l/kg in normal subjects to approximately 1.6 l/hr/kg and 91 l/kg in azotemic patients. The smaller volume of distribution is consistent with a decrease in oxaprozin tissue binding in azotemia. The decreased plasma and tissue binding and lower Clint suggest that, in the treatment of azotemic patients with rheumatoid arthritis, the dose of oxaprozin should begin at 600 mg once a day.

Adult↗
PubMed1981

Renal disease, age, and oxazepam kinetics.

Effects of renal insufficiency and age on oxazepam kinetics were assessed in 13 normal subjects (21 to 72 yr old), four patients with renal insufficiency, and eight patients on hemodialysis. Normal intact oxazepam results were: mean elimination half-life (t1/2), 10 hr; area under the curve (AUC), 6.0 microgram.hr/ml; unbound oxazepam fraction (fup), 3.2%; maximum concentration of unbound oxazepam (Cmax,u), 16 ng/ml; and intrinsic (unbound drug) clearance (Clint), 2.9 l/hr/kg. Less than 1% of the dose was excreted intact in urine. Age differences had no influence on results. In renal insufficiency patients, t1/2 was prolonged to 25 hr, fup increased to 7%, and Cmax,u and Clint were unchanged. Volume of distribution of unbound oxazepam (Vu) increased, thereby prolonging t1/2. In dialysis patients, t1/2 was prolonged to 33 hr, fup increased to 6.2%, and Cmax,u and Clint again were unchanged. Oxazepam was undialyzable; since unbound oxazepam disposition kinetics are not altered, no dosage adjustment for patients is necessary.

Adult↗
PubMed1980

Metabolism and kinetics of oxaprozin in normal subjects.

Absorption, biotransformation, excretion, and kinetics of oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) were examined in subjects after an oral dose of 14C-oxaprozin alone as well as before, during, and after long-term administration of unlabeled drug. A single dose of 14C-oxaprozin was rapidly absorbed and the unchanged drug was essentially the only labeled substance in plasma. Recovery of radioactivity in excreta, mostly in urine, exceeded 90%. Major biotransformation routes were glucuronidation of the carboxyl group and hydroxylation of the phenyl rings followed by glucuronidation. Administration of unlabeled oxaprozin did not affect the absorption, qualitative, or quantitative metabolite profile, or recovery of 14C-oxaprozin. Following a single dose, the kinetic parameters for 14C and unchanged drug in plasma were nearly the same. A2-compartment model with first-order elimination adequately describes kinetic disposition. The slow clearance (Clp), 0.08 to 0.12 1/hr, was almost entirely due to biotransformation and the plasma half-lifes, which ranged from 49 to 69 hr, reflected the small Clp. The small volume of distribution (VD beta = 8 to 9 1) indicates limited extravascular distribution. Multiple doses of unlabeled drug, especially when given concurrently, increased the Clp of 14C-oxaprozin. This effect is apparently related to decreased binding of high concentrations of oxaprozin to plasma protein. As a result of increased Clp, steady-state levels are only 40% of levels predicted from the single-dose study.

Adult↗
PubMed1980

Pulmonary function in a typical case of Pickwickian syndrome.

Pulmonary function was studied in a patient with Pickwickian syndrome, before and after a weight reduction of 160 kg which was brought about by jejunoileal bypass surgery. After weight reduction, there was an increase in alveolar ventilation, lung volumes and respiratory flow rates. Arterial blood oxygen tension, arterial oxygen saturation, arterial carbon dioxide tension and pH also showed a significant improvement towards normal. These findings indicate that reduction of body weight is beneficial for Pickwickian syndrome patients. The improvement of pulmonary function was probably due to the improvement of the patient's respiratory mechanics.

Adult↗
PubMed1978

Respiratory function of blood of the avians.

Individual blood samples were collected from wing veins of eight adult pigeons, two adult chickens and four adult geese and were analyzed for oxygen dissociation curves by hemo-scan, an instrument measuring PO2 and O2 saturation simultaneously. The findings agree with the common belief that avian blood in general has a low affinity for oxygen. Blood pH, PCO2, concentration of 2,3-DPG, lactic acid, pyruvic acid, red blood cell, hemoglobin and hematocrit were also determined, the related parameters have been calculated. Normal values of those variables were reported and the possible effects of some of those parameters on oxygen affinity are postulated.

Animals↗
PubMed1977

Near-maximal exercise responses in health and disease in middle-aged Chinese men.

Cardiovascular, aerobic, and ventilatory responses to a multistage treadmill test of near-maximal exercise were determined in 208 middle-aged Chinese men to provide standards in health, and to identify differences in relation to hypertension, coronary heart disease, chronic pulmonary disease and stroke. Except in patients with hypertension, exercise duration was shortened and symptom-limited oxygen uptake was reduced in all disease groups. Unexpectedly, stroke patients exhibited lower heart rate responses to exercise than did patients with coronary heart disease.

Adult↗
PubMed1975

Seven-year follow-up of cardiovascular study and maximal exercise of Chinese men.

A seven-year follow-up in 1973 of a prospective cardiovascular study of 1820 initially, healthy, middle-aged Chinese men of 40-59 years of age identified 1745 (95.9%) known survivors, 49 (2.7%) interim deaths, and 26 (1.4) who could not be traced. Of the survivors, 1462 (83.8%) were re-examined, 292 (16.7%) had another treadmill test of maximal exercise, and 283 (16.2%) failed to return for re-examination. On the basis of interim surveillance of hospital admissions, questionnaires and re-examination, a greater incidence of noncardiovascular events (338 or 18.6%) than evidence of cardiovascular disease (220 or 12.1%) was found while the majority (1021 or 56.1%) remained healthy. Total mortality was 0.29 for men under 50 and 0.76 per 100 person-years for men of 50 or more years of age. Only nine, or 18.4% of the deaths were due to cardiovascular causes, and unexpectedly for this population sample, only three were attributed to stroke. When cardiovascular morbidity was related to presence of ST depression after maximal exercise, to hypertension at rest by WHO criteria, to both findings, or to absence of either on initial intake examination, incidence increased from 2.3% for NEITHER group, to 5.7% for ST group, to 11.9% for HT group, and to 25.0% for BOTH groups. Re-examination revealed more evidence of cardiovascular disease than did surveillance of hospital admissions. Additional to effects of aging and mild adiposity, longitudinal changes in blood pressure and ST depression, increasing in the NEITHER group, but less frequent in the other groups, showed some evidence of regression toward the mean, as well as emerging disease and the confounding effects of uncontrolled treatment of hypertension in many. The potential for prediction of subsequent cardiovascular morbidity or mortality appeared stronger for hypertension than for postexertional ST depression, although the two were additive in this population, which is more prone to hypertension and stroke but now is developing clinical manifestations of coronary heart disease more frequently.

Adult↗