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Biomedical subjects

F E Simons

Publications and source records attributed to F E Simons.

At least 37 records · Page 2Linked to original sources
PubMed1989

Formoterol, a new long-acting selective beta 2-adrenergic receptor agonist: double-blind comparison with salbutamol and placebo in children with asthma.

We compared the protective effect and duration of action of inhaled formoterol, a new, long-acting, selective beta 2-agonist, to inhaled salbutamol and placebo in a double-blind, randomized, crossover study in 16 children with asthma with a mean age of 10.3 +/- 0.4 years. Mean baseline FEV1 was 96 +/- 3% predicted and mean provocative concentration of methacholine (milligrams per milliliter) required to decrease FEV1 by 20% (PC20) was 0.81 +/- 0.25 mg/ml of methacholine. On the 4 study days, baseline FEV1 was within 10% of the FEV1 on visit 1, and baseline PC20 was within one doubling dose of visit 1. Each day patients inhaled either placebo, salbutamol, 200 micrograms, formoterol, 12 micrograms, or formoterol, 24 micrograms. FEV1 and PC20 were measured repeatedly during 12 hours. After placebo inhalation, mean FEV1 did not change significantly during 12 hours. After salbutamol inhalation, the mean FEV1 was significantly increased for less than 3 hours, but after formoterol inhalation, 12 or 24 micrograms, the mean FEV1 was significantly increased for 12 hours. After placebo treatment, mean PC20 did not change significantly. After salbutamol inhalation, mean PC20 was significantly increased for only 3 hours, but after formoterol inhalation, 12 or 24 micrograms, mean PC20 was significantly increased for 12 hours. Protection by formoterol, 12 and 24 micrograms at 12 hours, was equivalent to protection by salbutamol at 3 hours. Inhaled formoterol is a potent, long-acting bronchodilator and provides significantly better antiasthma protection than inhaled salbutamol.

Adrenergic beta-Agonists↗
PubMed1989

Pharmacokinetic and pharmacodynamic studies of the H1-receptor antagonist hydroxyzine in the elderly.

The pharmacokinetics and pharmacodynamics of the antipruritic H1-receptor antagonist hydroxyzine hydrochloride were studied in nine healthy, fasting subjects (mean age 69.5 +/- 3.7 years) who ingested a single dose of hydroxyzine syrup, 0.7 mg/kg (mean dose 49.0 +/- 6.7 mg). Blood samples were collected hourly for 6 hours, every 2 hours from 6 to 12 hours, at 24 hours, and then every 24 hours for 144 hours. At these times an intradermal injection of 0.01 ml of a 0.1 mg/ml histamine phosphate solution was performed, and wheal and flare areas were computed. The serum elimination t1/2 of hydroxyzine was 29.3 +/- 10.1 hours; the volume of distribution was 22.5 +/- 6.3 L/kg; the clearance rate was 9.6 +/- 3.2 ml/min/kg, and the AUC was 1383.1 +/- 1039.0 ng.hr/ml. The mean serum elimination t1/2 of cetirizine, the active metabolite of hydroxyzine generated in vivo, was 24.8 +/- 7.7 hours, not significantly different from that of the parent compound (p = 0.05). After a single dose of hydroxyzine the mean wheal and flare areas were significantly suppressed from 1 to 144 hours, compared with the mean predose wheal and flare sizes (p less than 0.01). Maximum wheal suppression, compared with all other wheals measured during the study, occurred from 4 to 10 hours, inclusive, and maximum flare suppression occurred from 2 to 72 hours, inclusive (p less than 0.01). Hydroxyzine has a long t1/2 and a large volume of distribution in the elderly. The suppressive effect on the wheal and flare after a single dose of hydroxyzine is also extremely prolonged, suggesting the possibility of enhanced H1-receptor activity in old age.

Age Factors↗
PubMed1989

Development of chronic airway hyperresponsiveness in ragweed-sensitized dogs.

We studied dogs neonatally sensitized to ragweed and their littermate controls at 4, 6, 8, 10, 12, and 15 mo of age. Acute allergic airway response to inhalation of ragweed in the sensitized dogs was marked (greater than 12-fold increase from base line) and reproducible at all times. Nonallergic airway responsiveness, measured as the concentration of acetylcholine required to increase airway resistance by 5 cmH2O.l-1.s (PC5), increased in sensitized and decreased in nonsensitized dogs from 4 to 15 mo of age (P less than 0.01). Before antigen, at 12 and 15 mo, sensitized dogs were significantly (P less than 0.05) more responsive to acetylcholine than controls. Six hours after antigen, sensitized dogs were 11-fold more responsive (P less than 0.005) than controls at those times. More eosinophils and mast cells and fewer macrophages (P less than 0.05) were present in bronchoalveolar lavage (BAL) from 12- and 15-mo-old sensitized dogs than their controls. BAL fluid histamine was higher (P less than 0.05) in sensitized than control dogs. Regression analysis revealed r = -0.75 (P = 0.003) between BAL mast cells and PC5 in sensitized dogs and R2 = 0.89 for PC5 and BAL mast cells, macrophages, and eosinophils. Neonatally sensitized dogs represent an excellent animal model in which to study the pathophysiology of asthma.

Airway Resistance↗
PubMed1989

Optimum pharmacological management of chronic rhinitis.

Pharmacological treatment of chronic rhinitis has greatly improved with the introduction of the relatively non-sedating H1-receptor antagonists such as terfenadine, astemizole, loratadine, and cetirizine, and the safe, highly efficacious topical glucocorticosteroids such as beclomethasone dipropionate, flunisolide, budesonide, fluocortin butyl, and triamcinolone acetonide. In patients whose chief complaint is rhinorrhoea, topical ipratropium bromide may be of value. Patients whose major symptom is nasal congestion will benefit from intermittent use of topically or orally administered decongestants. In patients with allergic rhinitis, sodium cromoglycate (cromolyn sodium) or nedocromil sodium applied topically intranasally have a moderate beneficial effect and are associated with a low incidence of adverse effects. Non-pharmacological treatment of chronic rhinitis cannot be ignored. Patients must avoid inhalation of cigarette smoke and other irritants. Patients with chronic allergic rhinitis should avoid antigens to which they have known sensitivity: in addition, selected patients with allergic rhinitis may benefit from immunotherapy with the offending antigen(s).

Chronic Disease↗
PubMed1988

Comparison of ipratropium solution, fenoterol solution, and their combination administered by nebulizer and face mask to children with acute asthma.

In a randomized, double-blind, parallel-group trial, 47 children with acute asthma received a combination of ipratropium bromide solution (250 micrograms) and fenoterol hydrobromide solution (625 micrograms), fenoterol solution (625 micrograms) alone, or ipratropium solution (250 micrograms) alone, administered by face mask and nebulizer, with the dose repeated 60 minutes later. The groups did not differ significantly with regard to age, pulmonary function at baseline, or any other variable. They were monitored at 30, 60, 90, and 120 minutes by use of a clinical score, oxygen saturation, and pulmonary function tests. At the end of the study, albuterol was administered to assess residual bronchoconstriction. Clinical scores improved significantly after treatment in all groups at all times compared with baseline. The greatest improvement in FEV1 was seen in the patients treated with ipratropium/fenoterol, whether considered as absolute change, change in percent predicted, or percent change from baseline. Ipratropium/fenoterol was significantly better than fenoterol alone only when considered as percent change from baseline. Improvement in flow at mid and low lung volumes was significantly greater for the ipratropium/fenoterol combination than for ipratropium alone; no significant differences were noted between ipratropium/fenoterol and fenoterol for flow at mid and low lung volumes. Treatment with albuterol did not significantly improve pulmonary function in the groups receiving ipratropium/fenoterol or fenoterol alone, but it did increase flow at all lung volumes in the group receiving ipratropium alone. No patient complained spontaneously of any adverse reactions, and no clinically significant changes in heart rate or systolic or diastolic blood pressures occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

Lack of subsensitivity to terfenadine during long-term terfenadine treatment.

Eleven healthy male volunteers ingested terfenadine, 60 mg, every 12 hours for 56 days. Compliance was monitored strictly throughout the study. Before the first terfenadine dose on day 0, and 12 hours after the evening terfenadine dose every seventh day and on randomly selected "unscheduled" days, wheal-and-flare areas were measured after intradermal injections of 0.01 ml of histamine phosphate (1.0 mg/ml and 0.1 mg/ml). On days 0, 28, and 56, six volunteers had skin tests hourly for 12 hours after the morning terfenadine dose. On all study days, serum terfenadine metabolite I concentrations were measured each time histamine skin tests were performed. On days 7, 14, 21, 28, 35, 42, 49, and 56, the mean areas of the histamine-induced wheals did not differ significantly from each other but were significantly decreased compared to the mean wheal area on day 0 (p less than 0.01). On these days, the mean areas of the histamine-induced flares also did not differ significantly from each other but remained significantly suppressed compared to the mean flare areas on day 0 (p less than 0.01). Wheal-and-flare suppression was noted in all unscheduled histamine skin tests performed 12 hours after the evening terfenadine dose. In the subgroup of volunteers who had hourly tests, on day 0, the mean wheal-and-flare areas were significantly suppressed from 2 to 12 hours after the dose, with maximal wheal suppression occurring at 5 hours (p less than 0.05) and maximal flare suppression occurring from 3 to 9 hours (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

H1 receptor antagonist treatment of chronic rhinitis.

In patients with chronic rhinitis, H1 receptor antagonists play an important role in relieving the symptoms of sneezing, itching, and rhinorrhea. New information about the pharmacokinetics and pharmacodynamics of first-generation H1 receptor antagonists such as chlorpheniramine has become available in the past few years. Comprehensive pharmacokinetic and pharmacodynamic studies of new relatively nonsedating H1 receptor antagonists such as terfenadine, astemizole, loratadine, and cetirizine are appearing. An understanding of the differences in pharmacokinetics and pharmacodynamics among H1 receptor antagonists is required for optimal use of these drugs.

Asthma↗
PubMed1988

Pharmacokinetics of enprofylline administered intravenously and as a sustained-release tablet at steady state in children with asthma.

The pharmacokinetics of enprofylline (3-propylxanthine) were studied in 10 children with asthma (mean age 7.9 years), after enprofylline 1 mg/kg given intravenously and after enprofylline 7.5 +/- 1.3 mg/kg given as a sustained-release tablet after 8 days of oral dosing twice daily. The mean +/- SD enprofylline serum elimination half-life was 1.06 +/- 0.20 hours, considerably shorter than the half-life reported in adults. The mean steady-state volume of distribution was 0.55 +/- 0.05 L/kg. The mean clearance rate was 0.44 +/- 0.06 L/hr/kg. The mean enprofylline serum concentration at steady state was 1.7 +/- 0.5 mg/L. The mean peak to trough ratio was 3.02 +/- 1.31. On the first and ninth study days, 87% +/- 8% and 90% +/- 16%, respectively, of the dose of enprofylline was recovered as unchanged drug in the urine. Enprofylline has a short half-life in children, but the sustained-release formulation provides stable serum concentrations and satisfactory relief of asthma throughout the 12-hour dosing interval.

Asthma↗
PubMed1988

Allergic rhinitis: recent advances.

Our understanding of the pathophysiology of allergic rhinitis is increasing as a result of the development of new research tools for investigation of patients with this disorder. The pharmacologic treatment of allergic rhinitis has been greatly improved by introduction of relatively nonsedating H1-receptor antagonists and potent, topically active, glucocorticosteroids. Immunotherapy for allergic rhinitis is also changing with the times. Patient selection criteria are becoming more strict, and the introduction of safer, modified allergens with decreased allergenicity and retained immunogenicity will be a major advance.

Administration, Topical↗
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↗