Biomedical subjects
Publications and source records attributed to F E Simons.
The author provides a well-detailed update on chronic rhinitis, the most common disease of the respiratory tract. Discussed are the anatomy and physiology of the nose, investigation of the patient, etiology, and treatment, including avoidance of provoking factors, pharmacologic therapy, and immunotherapy.
Explore the source record for details and available documents.
In a double-blind trial we compared the efficacy and safety of inhaled salbutamol (albuterol), nebulized with oxygen by face mask, and subcutaneous epinephrine in 40 children with acute asthma. No significant difference between salbutamol and epinephrine was seen at any time for clinical score, respiratory rate, heart rate, blood pressure. PaO2, PaCO2, FVC, FEV1, FEV1/FVC, or FEF25-75%. PaO2 remained unchanged after salbutamol but increased significantly (P less than 0.05) after epinephrine. No significant difference occurred between the groups for repeat treatment, admission on initial visit, return to emergency room, admission on return, or total admissions. Significantly (P less than 0.01) increased adverse effects were seen within the group given epinephrine. We conclude that inhaled nebulized salbutamol and subcutaneous epinephrine are equally effective. In view of the lack of adverse effects and noninvasiveness of inhaled salbutamol, we recommend its use for the treatment of acute asthma in children.
Explore the source record for details and available documents.
Theo-Dur, a sustained-release theophylline formulation, was administered every 12 hours for three months to ten asthmatic children aged 3 to 7 years, with no evidence of adverse reaction or tolerance. There was significant temporal variation in serum theophylline concentrations. The mean difference between the peak and trough concentrations was 6.5 micrograms/mL (range, 3 to 14 micrograms/mL) in a 12-hour period. Serum theophylline concentrations correlated well with pulmonary function test results. Nine or more hours after a Theo-Dur dose, some children needed additional bronchodilator treatment and had impairment of pulmonary function. We recommend that children aged 7 years or younger who are given Theo-Dur have monitoring of predose serum theophylline concentrations, symptoms, and signs, as many will require a dose frequency greater than every 12 hours.
In dissolution studies of whole and halved 100-mg sustained-release theophylline tablets, drug release from halved tablets was significantly higher. These differences were not reflected in the bioavailability studies. The area under the curve (AUC) mean absorption time and fraction-of-dose recovered in urine at 24 hr were not significantly different following the ingestion of whole or halved 100-mg tablets. The elimination rate constant, half-life, volume of distribution, plasma, and renal clearance values were consistent with values reported previously. Discrepancies were found in the 24-hr metabolite distribution as compared to literature values and may be accounted for by the age and health of the subjects and the frequency of dosing.
We studied the pharmacokinetics and antihistaminic effect of brompheniramine in seven normal adults. The mean peak serum brompheniramine concentration of 11.6 +/- 3.0 ng/ml occurred at a mean time of 3.1 +/- 1.1 hr. The mean serum half-life value was 24.9 +/- 9.3 hr, the mean clearance rate was 6.0 +/- 2.3 ml/min/kg, and the mean volume of distribution was 11.7 +/- 3.1 L/kg. The mean wheal size was significantly suppressed (p less than or equal to 0.1) at 3, 6, and 9 hr after the brompheniramine dose when mean concentrations ranged from 10.2 +/- 2.9 to 7.0 +/- 2.2 ng/ml. Significant suppression (p less than or equal to 0.05) of mean flare size was found from 3 to 48 hr after the brompheniramine dose, when mean concentrations ranged from 10.2 +/- 2.9 to 2.5 +/- 0.6 nl/ml. The mean pruritus score was significantly suppressed at 9 and 12 hr (p less than or equal to 0.1) and at 24 hr (p less than or equal to 0.05). Brompheniramine had a long half-life and large volume of distribution in normal adults. It also had a prolonged antihistaminic effect in the skin as evidenced by suppression of the wheal and flare response to histamine and by suppression of pruritus.
Chlorpheniramine is widely used, but there is very little information about its pharmacokinetics and efficacy in children. In 11 patients with allergic rhinitis, ages 6 to 16 yr, we found a mean serum chlorpheniramine half-life of 13.1 +/- 6.3 hr, a mean volume of distribution of 7.0 +/- 2.8 L/kg, and a mean clearance rate of 7.2 +/- 3.2 ml/min/kg. Suppression of symptoms and signs of allergic rhinitis and suppression of the histamine-induced wheal and flare responses occurred when mean serum chlorpheniramine concentration ranged from 2.3 to 12.1 and 4.1 to 10.0 ng/ml, respectively. This combined with the large volume of distribution for the drug, suggest that tissue binding is an important aspect of chlorpheniramine pharmacokinetics.
In a 6 1/2-month-old infant with hepatic failure secondary to hereditary tyrosinemia, the theophylline clearance rate of 0.016 liter/kg/h was reduced for age and the serum half-life was prolonged to 18.0 h. Theophylline, 3.4 micrograms/ml, and caffeine, 2.2 micrograms/ml, were identified in a urine sample obtained 48 h after the test dose of theophylline, but no 1-methyluric acid, 1,3-dimethyluric acid or 3-methylxanthine were detected. This is the first infant with liver dysfunction and impaired theophylline disposition to be reported.
Ketotifen, an orally active, prophylactic anti-asthmatic drug, was compared with placebo in a double-blind, three-month parallel-group trial in 20 children. Children receiving ketotifen were more likely to reduce concomitant medications and had significant improvement over time in asthma scores and mean flows at 75%, 50%, and 25% of vital capacity. They also had a significantly increased incidence of dry mouth and significant weight gain compared to those receiving placebo. In some children with asthma, ketotifen may be a useful alternative to existing drugs.
In a double-blind dose response study in 26 children, 3, 6, or 12 microgram/kg of terbutaline sulfate was compared with 10 microgram/kg of epinephrine administered subcutaneously. In the first hour after injection, all doses of terbutaline and epinephrine resulted in improvement in mean clinical score, mean forced vital capacity, mean forced expiratory volume in the first second, and mean forced expiratory flow from 25% to 75% of vital capacity. Terbutaline epinephrine. However, while adverse effects following terbutaline were clinically imperceptible, epinephrine produced unpleasant headache and excitement in a few patients. Terbutaline did not change mean PaO2 or PaCO2 significantly in a subgroup of patients. The 12 microgram/kg dose of terbutaline was superior to 3 or 6 microgram/kg in relieving obstruction to airflow measured at the midportion of the vital capacity. This dose caused tremor in some children, but the tremor was not apparent to patients or their parents.
Theophylline is a safe, effective drug for the treatment of apnea of prematurity. The pharmacokinetics of theophylline have been studied extensively in preterm neonates. There is some inter-infant variability, but generally, compared to children and adults, prolonged half-life values and low clearance rates have been found: the apparent volume of distribution is larger and protein binding of the drug is decreased. A unique pattern of metabolism involving methylation to caffeine has been identified. Theophylline maintenance dose requirements are much lower in neonates than in children. When therapy is begun, a useful guide is to give a loading dose of 5 mg/kg anhydrous theophylline followed by maintenance doses of 2 mg/kg every 12 hr. In many infants, this will suffice to prevent apnea without producing signs of toxicity. After commencement of therapy, doses must be individualized for each infant on the basis of serum theophylline concentration monitoring and monitoring for apnea. Evidence of theophylline toxicity in neonates may be subtle, and only scanty data are available regarding possible long-term effects of chronic theophylline treatment of neonates.
The pharmacokinetics of theophylline were studied in 1-month-old term infants who received accidental overdoses of theophylline during treatment for bronchiolitis. Both infants survived without neurologic sequelae. Elimination half-life values of 14.5 and 15.2 hours, respectively, were shorter than reported in premature infants but longer than in infants aged 3 months or older. Caffeine appeared in the sera of both patients, who had not received it in any form. In term infants, elimination of theophylline may occur by N-methylation in contrast to older patients in whom the drug is chiefly eliminated by demethylation and oxidation. Theophylline has not been proved effective for the treatment of bronchiolitis. It should be used with caution for wheezing in very young infants until its pharmacokinetics have been studied further in nontoxic, full-term infants younger than age 3 months.
In this prospective study, chest radiographs were obtained in 23 children during 33 acute asthmatic episodes. The degree of hyperinflation was assessed radiologically by three methods and compared to the clinical findings. There was no correlation between the radiologic impression of hyperinflation and the clinical severity of the asthmatic episode.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Theophylline protein binding was 58-82% in serum from six normal adults and 42 asthmatic patients, 1-25 years old, who were given 5 mg of theophylline/kg. The binding range was greatest in young patients, but the proportion of protein-bound drug did not correlate with age. Theophylline protein binding was higher than previously reported. The effect of binding should be considered in patients who do not have optimal bronchodilation from theophylline despite total serum theophylline concentrations of 10-20 microgram/ml.
The pharmacokinetics and urinary excretion of a single dyphylline dose were studied in five normal volunteers. The mean dyphylline half-life was 1.8 +/- 0.2 hr; the mean total body clearance rate and mean renal clearance rate were 333 +/- 62 and 276 +/- 52 ml/min, respectively; and the mean volume of distribution was 0.8 +/- 0.2 liter/kg. In the urine, 83 +/- 5% of the dose was excreted as unchanged drug, and theophylline was not detected. Dyphylline doses of 19--27 mg/kg, resulting in peak serum dyphylline concentrations of 19.3--23.5 micrograms/ml, were tolerated well by four subjects. One subject had a severe headache following a 28-mg/kg dose, associated with a peak serum dyphylline concentration of 36.4 micrograms/ml. This study confirms speculation that dyphylline is not metabolized to theophylline in vivo.