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Biomedical subjects

F E Simons

Publications and source records attributed to F E Simons.

At least 91 records · Page 5Linked to original sources
PubMed1987

The effect of chronic administration of hydroxyzine on hydroxyzine pharmacokinetics in dogs.

Subsensitivity to H1-receptor antagonists has been attributed to autoinduction of enzyme systems and increased clearance rates during chronic drug administration. We studied the changes in serum half-life values and clearance rates in dogs who were administered hydroxyzine, 0.7 mg/kg, intramuscularly, daily, for 150 days. Pharmacokinetic studies were performed on the first day of drug administration, and on days 30, 60, 90, 120, and 150. The mean serum half-life value on day 30, 60, and 120 was significantly longer (p less than 0.05) than that of 2.4 +/- 0.3 hours obtained on day 1. The mean clearance values obtained on days 30, 60, 90, 120, and 150 were significantly slower (p less than 0.05) than the value of 25.12 +/- 4.13 ml/min/kg obtained on day 1 but were not significantly different from each other. Mean serum hydroxyzine concentrations were often significantly higher on the later study days than on day 1. The mean apparent volume of distribution values obtained on days 30, 60, 90, 120, and 150 did not differ significantly from the value of 5.0 +/- 1.5 L/kg obtained on day 1. This study adds to the mounting evidence that subsensitivity to the effects of an H1-receptor antagonist is not due to autoinduction of enzyme systems, more rapid clearance of the drug, and lower concentrations of the drug in serum and tissue.

Animals↗
PubMed1987

The pharmacokinetics and pharmacodynamics of terfenadine in children.

The pharmacokinetics and pharmacodynamics of terfenadine were studied in 13 children with allergic rhinitis, mean age 7.45 +/- 0.54 SEM years. Serum concentrations of the active carboxylic acid metabolite of terfenadine (terfenadine metabolite I) were measured before and hourly for 8 hours after administration of a single dose of terfenadine suspension. The mean maximum serum concentration of terfenadine metabolite I, 242 +/- 28 ng/ml, occurred at 2.3 +/- 0.2 hours; the mean serum half-life value was 2.0 +/- 0.1 hours. Wheals and flares after epicutaneous tests with histamine phosphate, 1.0 mg/ml and 0.2 mg/ml, were significantly suppressed from 1 to 8 hours after the terfenadine dose compared to predose values. Maximum wheal suppression occurred at from 3 to 6 hours. Itching was completely suppressed for 8 hours. No serious adverse effects occurred. Terfenadine in children appears to be well absorbed, and its carboxylic acid metabolite has a short serum elimination half-life. The duration of its suppressive effect on the histamine-induced wheal and flare greatly exceeds that expected from consideration of serum terfenadine metabolite I concentrations.

Benzhydryl Compounds↗
PubMed1987

The comparative pharmacokinetics of H1-receptor antagonists.

H1-receptor antagonists appear to be absorbed rapidly after oral administration, with peak serum concentrations being reached one to three hours after a dose. For most of these drugs, the absolute bioavailability is unknown because no intravenous formulations are available for comparative purposes. The serum elimination half-life values of these agents are variable: a few hours for terfenadine and triprolidine; about 9 hours for cetirizine, azatadine, and loratadine; from 20 to 25 hours for hydroxyzine, chlorpheniramine, and brompheniramine; and from 5 to 14 days for astemizole. Few pharmacokinetic studies of H1-receptor antagonists in children have been reported. However, it is known that chlorpheniramine, hydroxyzine, cetirizine, and terfenadine have shorter elimination half-life values in children than in adults. Regardless of the age of patients, for most of the H1-receptor antagonists the apparent volumes of distribution and total body clearances appear to be large (3.4 to 18.5 L/kg and 4.4 to 32.1 mL/min/kg, respectively). Cetirizine is an exception, with values of 0.8 L/kg and 0.5 mL/min/kg. Urinary excretion of unchanged antihistamine is higher after cetirizine (60% of dose) than any other H1 blocker. For H1-receptor antagonists with long half-life values, steady state may not be reached for several days (chlorpheniramine and brompheniramine) or several weeks (astemizole), and significant accumulation of drug occurs if the dosing interval is more frequent than every half-life. There is no evidence for the introduction of metabolism of H1-receptor antagonists, even after months of treatment.

Adult↗
PubMed1986

Sustained-release terbutaline vs sustained-release theophylline in young patients with asthma.

Twenty patients with asthma (mean age, 10.9 +/- 2 years) entered a six-week, randomized, double-blind, crossover comparison of sustained-release (S-R) terbutaline sulfate (Bricanyl Durules) vs S-R theophylline (Theo-Dur). In each two-week study period each patient received S-R theophylline twice daily in doses previously adjusted to give serum theophylline concentrations in the range of 10 to 20 mg/L (56 to 111 mumol/L); or S-R terbutaline sulfate, 5 mg twice daily; or S-R terbutaline sulfate, 7.5 mg twice daily. All treatment regimens produced significant improvement in one or more pulmonary function test values compared with prestudy values. The incidence of acute asthma episodes were similar during each treatment regimen. No clinically significant difference occurred between the regimens for daily symptom scores, peak expiratory flow rates, or use of a terbutaline metered-dose inhaler. At the end of the theophylline treatment period, the mean (+/- SD) theophylline level 12 to 14 hours after the last dose was 10.1 +/- 3.3 mg/L (56 +/- 18 mumol/L); at the end of the terbutaline treatment periods, the mean trough terbutaline levels were 2.22 micrograms/L (9.9 +/- 4.4 nmol/L) (S-R terbutaline sulfate, 5 mg twice daily) and 3.07 micrograms/L (13.7 +/- 5.4 nmol/L) (S-R terbutaline sulfate, 7.5 mg twice daily). Adverse effects, including tremor, occurred with similar frequency during all three drug regimens. Sustained-release formulations of theophylline and terbutaline, in the dosages studied, provided comparable control of asthma symptoms.

Adolescent↗
PubMed1986

An investigation of the H1-receptor antagonist triprolidine: pharmacokinetics and antihistaminic effects.

A single oral dose of triprolidine hydrochloride, 0.04 mg/kg (mean dose 2.7 +/- SD 0.4 mg) was administered to seven healthy, fasting adult volunteers who had never been treated previously with H1-receptor antagonists. Blood sampling and intradermal tests with 0.01 ml of histamine phosphate (0.1 mg/ml) were performed at -0.25, 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours after the dose. Wheal-and-flare circumferences were traced, and the areas were measured by planimetry. Pruritus was quantitated by use of a clinical score. Urine was collected in 6-hour pooled aliquots for a total of 24 hours. Serum and urine triprolidine concentrations were measured by high-performance liquid chromatography. Wheal-and-flare areas and pruritus decreased after the triprolidine dose. Suppression of mean flare size was statistically significant at 2, 3, 6 and 8 hours. Suppression of mean wheal size was not statistically significant at any time compared to predose values. The mean triprolidine serum half-life was 2.1 +/- 0.8 hours. The mean peak serum triprolidine concentration of 15.4 +/- 8.3 ng/ml occurred 2 hours after ingestion. No triprolidine was detected in the serum after 12 hours. The mean urinary excretion of unchanged triprolidine during 24 hours was 1.3 +/- 1.0% of the dose administered.

Adult↗
PubMed1986

Comparison of the suppressive effect of astemizole, terfenadine, and hydroxyzine on histamine-induced wheals and flares in humans.

Thirty-two healthy volunteers completed a 14-day, double-blind, noncrossover study comparing the efficacy and adverse effects of astemizole, terfenadine, and hydroxyzine. The subjects received either astemizole (load), 30 mg once daily for 1 week and then 10 mg once daily for 1 week, or astemizole (no load), 10 mg once daily for 2 weeks, or terfenadine, 60 mg twice daily for 2 weeks, or hydroxyzine, 50 mg once daily for 2 weeks. Before and on days 7 and 14 of treatment, five intradermal tests with various amounts of histamine phosphate (range 0.3 to 40 micrograms) were performed. Wheal-and-flare responses were traced, and the areas were computed by use of a graphics tablet. All four H1-receptor antagonist treatment regimens were equally effective in reducing the flare response to histamine. Astemizole (load) and hydroxyzine were significantly more effective than terfenadine and astemizole (no load) in reducing wheal size. The incidence of adverse effects, including sedation, was low overall and lowest in the astemizole (no load) and terfenadine groups, although this difference was not statistically significant.

Adult↗
PubMed1985

The bronchodilator effect and pharmacokinetics of theobromine in young patients with asthma.

The bronchodilator effect of a 10 mg/kg dose of theobromine (3,7-dimethylxanthine) was compared with that of 5 mg/kg of theophylline (1,3-dimethylxanthine) in young patients with asthma. Bronchodilation, as assessed by forced vital capacity, forced expiratory volume in the first second, forced expiratory flows at 25%, 50%, and 75% of vital capacity, and percent of forced expiratory volume in the first second/forced vital capacity did not differ significantly between the two drugs. After each drug bronchodilation peaked at 2 hours and lasted for 6 hours, although it was not always statistically significant for theobromine. The mean peak serum concentrations of both drugs, the time at which peak serum concentrations occurred, and elimination half-life values were similar for theobromine and theophylline.

Adolescent↗
PubMed1985

Terbutaline by metered-dose inhaler: conventional inhaler versus tube spacer for children with asthma.

We compared terbutaline administered through an 80-mL, 10 X 3.2-cm tube spacer versus a conventional metered-dose inhaler in 34 asthmatic patients, aged 8 to 16 years. In this double-blind, single-dose study, three groups of children (spacer active, conventional active, and placebo) were assessed clinically and with spirometry before and at one-half hour intervals for two hours after therapy. One investigator taught inhaler use and monitored patients' errors in technique. Compared with placebo, terbutaline delivered by either the tube spacer or the conventional inhaler significantly improved pulmonary function from one-half to two hours after treatment. Both the spacer and conventional inhaler were equally effective in improving pulmonary function from the baseline state. Only 4/34 (11.7%) children used both inhalers without any error. Adverse effects were mild, transient, and infrequent and did not differ between the groups. Terbutaline aerosol, whether delivered by the tube spacer or conventional actuator, provides effective bronchodilation for children with asthma, in spite of frequent errors in technique of inhaler use.

Aerosols↗
PubMed1984

The bronchodilator effects and pharmacokinetics of caffeine in asthma.

We compared the bronchodilator effects and pharmacokinetics of orally administered caffeine (10 mg per kilogram of body weight) and theophylline (5 mg per kilogram) in a double-blind, single-dose study in asthmatic patients 8 to 18 years of age. After 48 hours of withdrawal of all methylxanthines, 13 patients received caffeine and 10 received theophylline. Significant improvements in forced vital capacity, forced expiratory volume in one second, and forced expiratory flow rates occurred from one to six hours after administration of either caffeine or theophylline. The bronchodilator effect of caffeine did not differ significantly from that of theophylline and was maximal two hours after ingestion of each drug. Peak serum levels of caffeine (13.5 +/- 2.9 mg per liter) occurred at one hour, and peak levels of theophylline (8.4 +/- 1.7 mg per liter) at 2.2 +/- 0.8 hours. The mean serum half-time for caffeine was 3.9 +/- 1.4 hours and that for theophylline was 5.8 +/- 1.7 hours. All patients receiving caffeine metabolized it to paraxanthine, theobromine, and theophylline. Mild, transient side effects were seen after both caffeine and theophylline. Vital signs did not change significantly after either drug. We conclude that caffeine, a commonly available chemical, is an effective bronchodilator in young patients with asthma.

Adolescent↗
PubMed1984

The pulmonary index. Assessment of a clinical score for asthma.

We used a clinical score, the pulmonary index (PI), in the emergency room assessment of children with acute asthma. The PI was derived from respiratory rate, wheezing, inspiratory-expiratory ratio, and use of accessory muscles. Patients were treated with a beta-adrenergic drug and were assessed before and at 15-minute intervals after treatment using clinical examination, PI, and spirometry. The PI before treatment correlated significantly with the mean percent of forced expiratory volume in the first second to forced vital capacity ratio. The PI 30 minutes after treatment correlated significantly with all tests of pulmonary function performed. The PI is a simple score that is easily derived from clinical observation.

Acute Disease↗
PubMed1984

Urinary excretion of chlorpheniramine and its metabolites in children.

The pharmacokinetics and urinary excretion of chlorpheniramine were studied in 11 patients, aged 6-16 years, with allergic rhinitis. In these children, chlorpheniramine had a mean elimination half-life of 13.1 +/- 6.6 h, a mean clearance rate of 7.23 +/- 3.16 mL/min/kg, and a mean apparent volume of distribution of 7.0 +/- 2.8 L/kg. Over 48 h, the recovery in urine was as follows: chlorpheniramine, 11.3 +/- 6.7%; demethylchlorpheniramine , 23.3 +/- 11.1%; and didemethylchlorpheniramine , 9.6 +/- 9.4%. Urine flow rate and urine pH were uncontrolled and ranged from 2.2 to 113.3 mL/h and 5.1-7.9, respectively, over the 48-h period. In some children urine flow rate and pH were constant, while in others there was great variability. When drug and metabolite excretion rates versus both urine flow rates and pH values were analyzed by multiple linear regression, the results were significantly better (p less than or equal to 0.05) than when each factor was analyzed independently. The excretion rate of chlorpheniramine and its two demethylated metabolites decreased as urine pH increased and urine flow rate decreased. This information must be considered in future pharmacokinetic studies of this drug.

Adolescent↗
PubMed1984

Dissolution studies of some sustained-release theophylline dosage forms.

Dissolution studies were carried out with the USP rotating-basket apparatus in both simulated gastric and intestinal fluids. Four different brands of sustained-release theophylline products of different strengths (nine formulations) were studied. The percentage of the dose released in 1 h in gastric fluid ranged from (mean +/- SD) 6.6 +/- 0.9 to 50.1 +/- 3.8%. By 6 h, the percentage of the dose released ranged from 10.8 +/- 1.8 to 86.5 +/- 5.2%. Similar formulations of different strengths released significantly different fractions of their dose at respective sampling times. In intestinal fluid, some formulations released 100% of their dose within 3-4 h, behaving more like enteric-coated preparations. One dosage form appeared to release drug by an apparent zero-order rate. From one brand of theophylline (two strengths), only 48.1 +/- 5.6 and 29.9 +/- 4.1% of label strength, respectively, dissolved in 25 h in intestinal fluid. Some of these in vitro results were rank-correlated to previously reported bioavailability and pharmacokinetic studies.

Biological Availability↗
PubMed1984

Pharmacologic treatment of rhinitis.

Major improvements in the quality of recent pharmacologic studies of rhinitis are evident. In many of the studies, the criteria for patient selection are being more carefully described and patients with allergic rhinitis, nonallergic rhinitis with eosinophilia, and vasomotor rhinitis are no longer grouped together. In most studies, efficacy is still being ascertained by subjective symptom scores, although in some of the challenge studies, investigators are making noble attempts to quantitate symptoms objectively, eg, amount of secretions, sneezing, and even itching of the nares. Although nasal congestion is only one symptom of chronic rhinitis, the various methods of measuring nasal resistance by rhinometry are increasingly well described and standardized. General concepts that are emerging from the vast literature on pharmacologic treatment of rhinitis are as follows: 1) The much-maligned H1 receptor antagonists may actually be more useful than previously thought, once further information about how to use them optimally is available. Interesting new antihistamines are being developed. Further investigations of allied drugs such as the tricyclic antidepressants (doxepin) are definitely in order. 2) alpha-adrenergic agonists definitely have short-term usefulness but side effects from this class of drugs have, if anything, been underestimated. Exploration of the use of beta-adrenergic agonists and anti-cholinergics in the treatment of chronic rhinitis has begun. 3) Disodium cromoglycate is not universally effective in chronic rhinitis, perhaps in part because compliance with a prophylactic drug requiring insufflation four or six times daily may not be high. The degree of response and the percentage of patients having an excellent response to the drug is lower than for the new corticosteroids. 4) Topical corticosteroids administered intranasally are clearly the most effective medications for treatment of chronic rhinitis. Further study of the benefit versus the long-term risk of these drugs is mandatory, but their remarkable efficacy and safety in the treatment of chronic rhinitis is undisputed. Some comparisons between the four major groups of drugs are now being made, and further attempts to define the relative roles and the interactions of drugs used in the pharmacologic treatment of rhinitis are definitely needed.

Adrenal Cortex Hormones↗
PubMed1984

The pharmacokinetics and antihistaminic of the H1 receptor antagonist hydroxyzine.

We studied the pharmacokinetics and the suppression of histamine-induced wheals, flares, and pruritus in the skin after administration of the histamine H1 antagonist hydroxyzine to seven healthy adults. After a single oral dose of hydroxyzine, 0.7 mg/kg (mean dose 39.0 +/- 5.4 mg), the mean maximum serum hydroxyzine concentration of 72.5 +/- 11.1 ng/ml occurred at a mean time of 2.1 +/- 0.4 hr. The mean elimination half-life calculated from the terminal linear portion of the serum hydroxyzine concentration vs. time curve was 20.0 +/- 4.1 hr. The mean clearance rate was 9.78 +/- 3.25 ml/min/kg and the mean volume of distribution was 16.0 +/- 3.0 L/kg. The single dose of hydroxyzine suppressed pruritus at the wheal and flare sites from 1 to 36 hr. Maximal suppression of the wheals was 80% and maximal suppression of the flares was 92%. Significant suppression of the wheals and flares persisted for 36 and 60 hr, respectively. Pharmacodynamic analysis of the wheal and flare suppression data and the mean serum hydroxyzine concentrations supports the prolonged terminal serum half-life value for the drug.

Adult↗
PubMed1984

Pharmacokinetics and antipruritic effects of hydroxyzine in children with atopic dermatitis.

We studied the pharmacokinetics and antipruritic effects of hydroxyzine hydrochloride in 12 children, mean age 6.1 +/- 4.6 years, with severe atopic dermatitis. After a single 0.7 mg/kg orally administered dose of the drug, the mean peak serum hydroxyzine concentration of 47.4 +/- 17.3 ng/ml occurred at a mean time of 2.0 +/- 0.9 hours. The mean elimination half-life was 7.1 +/- 2.3 hours, the mean clearance rate was 32.08 +/- 11.05 ml/min/kg, and the mean apparent volume of distribution was 18.5 +/- 8.6 L/kg. The elimination half-life increased with increasing age (r = 0.83). Pruritus was significantly suppressed from 1 to 24 hours after the administration of the dose, with greater than 85% suppression from 2 to 12 hours. The only adverse effect reported was sedation. In a subsequent double-blind, crossover, multiple-dose study of 2 weeks' duration, hydroxyzine 0.7 mg/kg three times daily was as effective as hydroxyzine 1.4 mg/kg three times daily in relieving pruritus and promoting resolution of the skin lesions. The 0.7 mg/kg tid dose caused significantly less sedation than the 1.4 mg/kg tid dose.

Antipruritics↗
PubMed1984

Chronic rhinitis.

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.

Adolescent↗
PubMed1983

Inhaled salbutamol (albuterol) vs injected epinephrine in the treatment of acute asthma in children.

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.

Acute Disease↗