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Biomedical subjects

F E Simons

Publications and source records attributed to F E Simons.

At least 73 records · Page 4Linked to original sources
PubMed1990

Recent advances in H1-receptor antagonist treatment.

The second-generation H1-receptor antagonists terfenadine, astemizole, loratadine, and cetirizine are important first-line drugs for the relief of symptoms in patients with allergic rhinoconjunctivitis or chronic urticaria and may eventually supplant the potentially sedating first-generation H1-receptor antagonists in the treatment of these disorders. Terfenadine, astemizole, loratadine, and cetirizine produce an incidence of central nervous system and anticholinergic adverse effects similar to that produced by placebo. Our ability to use H1-receptor antagonists optimally has been greatly enhanced by recent pharmacokinetic and pharmacodynamic studies of these medications.

Astemizole↗
PubMed1990

New H1-receptor antagonists: clinical pharmacology.

The non-sedating, second-generation H1-receptor antagonists such as terfenadine, astemizole, loratadine and cetirizine differ considerably from each other in their pharmacokinetics and pharmacodynamics. They are generally well absorbed when administered orally. They have extremely variable serum elimination half-life values. The maximum antihistaminic effect of these medications occurs several hours later than peak serum concentrations do. The duration of the antihistaminic effect is much longer than would be predicted from the serum elimination half-life values. The relative incidence of anticholinergic and central nervous system adverse effects caused by these medications is similar to that produced by placebo. The introduction of the second-generation H1-receptor antagonists represents a major advance in symptomatic therapy of allergic disorders such as allergic rhinitis and urticaria.

Histamine H1 Antagonists↗
PubMed1990

A double-blind, single-dose, crossover comparison of cetirizine, terfenadine, loratadine, astemizole, and chlorpheniramine versus placebo: suppressive effects on histamine-induced wheals and flares during 24 hours in normal subjects.

We objectively tested the relative antihistaminic effects of cetirizine, 10 mg; terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg; astemizole, 10 mg; chlorpheniramine, 4 mg; and placebo in healthy, male volunteers, mean age 25 +/- 4 years, and mean weight, 73 +/- 9 kg. The wheal areas and flare areas produced by epicutaneous tests with histamine phosphate, 1 mg/ml, before ingestion of the H1-receptor antagonist or placebo, and afterward, at 0.3 and 0.7 hours, then hourly from 1 to 12 hours and at 24 hours, were traced at 10 minutes and measured with an IBM-PC digitizer and stereometric software. In this experimental model, the H1-receptor antagonists differed significantly with regard to time of onset of action, amount of suppression of the histamine-induced wheal and flare, and duration of action. The rank order was, from most effective to least effective, cetirizine, 10 mg; terfenadine, 120 mg; terfenadine, 60 mg; loratadine, 10 mg; astemizole, 10 mg; chlorpheniramine, 4 mg; and placebo.

Adult↗
PubMed1989

The pharmacokinetics and pharmacodynamics of hydroxyzine in patients with primary biliary cirrhosis.

Hydroxyzine, a potent H1-receptor antagonist often used for relief of pruritus in patients with hepatic dysfunction, was studied in eight patients, mean age 53.4 +/- SD 11.2 years, with primary biliary cirrhosis. The patients ingested a single dose of hydroxyzine, 0.7 mg/kg (mean dose 43.9 +/- 6.6 mg). Before the dose, then hourly for 6 hours, every 2 hours from 6-12 hours, at 24 hours, and every 24 hours for 6 days, serum hydroxyzine and cetirizine were measured and an intradermal injection of 0.01 mL of a 0.1 mg/mL solution of histamine phosphate was performed. Wheals and flares were traced at 10 minutes and the areas were calculated. Mean peak hydroxyzine levels of 116.5 +/- 60.6 ng/mL occurred at 2.3 +/- 0.7 hours and mean peak cetirizine levels of 500.4 +/- 302.0 ng/mL occurred at 4.8 +/- 2.8 hours. The mean serum elimination half-life of hydroxyzine was 36.6 +/- 13.1 hours, and the mean serum elimination half-life of cetirizine was 25.0 +/- 8.2 hours. The mean hydroxyzine clearance rate was 8.65 +/- 7.46 mL/min/kg, and the mean volume of distribution was 22.7 +/- 13.3 L/kg. The mean wheal area was suppressed (P less than 0.01) from 1 to 120 hours, with maximal suppression from 2 to 48 hours. The mean flare area was suppressed from 1 to 144 hours, with maximal suppression from 3 to 24 hours (P less than 0.01). All patients became sleepy from 0.5 to 6 hours. Blurred vision, dizziness and dry mouth each occurred in two patients. Hydroxyzine elimination is impaired in patients with primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Cetirizine: a pharmacokinetic and pharmacodynamic evaluation in children with seasonal allergic rhinitis.

In a double-blind, randomized, parallel-group 5-week study, cetirizine, 5 mg or 10 mg daily, was ingested by 10 and nine children, respectively. Cetirizine was rapidly absorbed with mean peak cetirizine concentrations of 427.6 +/- SD, 144.2 ng/ml, 1.4 +/- 1.1 hours after the 5 mg dose, and 978.4 +/- 340.6 ng/ml, 0.8 +/- 0.4 hours after the 10 mg dose. The dose-independent serum-elimination half-life of cetirizine was 7.1 +/- 1.6 hours after cetirizine, 5 mg, and 6.9 +/- 1.6 hours after cetirizine, 10 mg. Urinary excretion of unchanged cetirizine during 24 hours after the initial dose of cetirizine, 5 mg, was 40 +/- 15%, and after cetirizine, 10 mg, it was 39 +/- 14%. The mean histamine-induced wheal-and-flare areas were significantly suppressed from 1 to 24 hours after the first dose of cetirizine, 5 mg, and from 1/2 to 24 hours after the first dose of cetirizine, 10 mg, compared to the mean predose wheal-and-flare areas (p less than 0.01). During daily dosing with cetirizine, 5 mg or 10 mg at bedtime for 35 days, serum cetirizine concentrations and suppression of histamine-induced wheals and flares were monitored every 7 days, 12 hours after the cetirizine dose. The mean serum cetirizine concentrations remained relatively stable during this time, and the mean wheal-and-flare areas remained significantly suppressed (p less than 0.01) compared to baseline wheal-and-flare areas measured before the first dose of cetirizine. The symptoms and signs of allergic rhinitis were suppressed throughout the study by cetirizine, 5 mg and 10 mg.(ABSTRACT TRUNCATED AT 250 WORDS)

Cetirizine↗
PubMed1989

H1-receptor antagonists: clinical pharmacology and therapeutics.

Each H1-receptor antagonist has unique pharmacokinetic and pharmacodynamic properties, and each H1-antagonist has unique potency and potential for causing adverse effects. Some of the first-generation H1-receptor antagonists should no longer be used because their relative lack of efficacy is combined with a high potential for causing adverse effects. Some of the new H1-receptor antagonists, in manufacturers' recommended doses, seldom cause sedation but may have only modest potency. The choice of optimal H1-receptor antagonist treatment for each patient should be based on up-to-date clinical pharmacology information.

Chemical Phenomena↗
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↗