Uniphyl Tablets Research Articles

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Twenty-one patients, 12 to 18 years of age, with nocturnal asthma controlled with sustained-release theophylline administered twice daily, were enrolled in a 10-week, double-blind, two-way crossover study that compared Theo-Dur tablets administered twice daily with an equivalent daily dose of Uniphyl tablets administered once daily at bedtime. Seventeen patients completed the study. The mean morning theophylline serum level obtained with Uniphyl tablets was significantly higher than that obtained with Theo-Dur tablets (13.1 versus 9.6 μg/ml, p = 0.02). The mean evening serum level was significantly lower with Uniphyl tablets (6.3 versus 10.1 μg/ml, p = 0.003). Despite these differences in serum concentrations, morning and evening pulmonary function test values (forced expiratory volume in one second and peak expiratory flow rate) and symptom scores were nearly identical for the two preparations, as was the supplemental use of aerosol bronchodilators. Once-daily dosing with Uniphyl tablets may benefit adolescent patients with nocturnal asthma by increasing compliance and providing better asthma control. In addition, the lower daytime theophylline levels produced by this preparation may also reduce long-term adverse effects on behavior and cognition.

Once-daily evening administration of Uniphyl tablets: announcement of first available chronotherapy of nocturnal asthma.

Theophylline chronotherapy recently became a reality for patients with reversible airways disease. UniphylR 400 mg tablets (controlled-release theophylline, the Purdue Frederick Company, Norwalk, Connecticut) are now indicated for once-daily evening administration, both in the United States and Canada. This development follows the previous use of Uniphyl tablets in once-daily morning doses and marks the first-available antiasthmatic treatment in North America to incorporate dosing time as an important therapeutic dimension. It reflects increasing recognition, by the medical community, of the need to consider the individual patient's timing of symptoms in relation to the kinetics of the drug.

The clinical significance of food-induced changes in the absorption of theophylline from Uniphyl tablets

To determine the effects of food on the absorption of theophylline from Uniphyl tablets (a once-daily sustained-release theophylline formulation), we performed a crossover evaluation in 20 adults with asthma. After 5 days of continuous dosing (at 6 pm), all patients received their regular Uniphyl dose under specified fasting conditions, and serum theophylline concentrations were measured sequentially during the following 24 hours. The patients' next Uniphyl dose was administered immediately after ingestion of a standardized high-fat meal, and theophylline concentrations were again measured during 24 hours. Five days later, the procedure was repeated in the opposite order. The patients' mean daily theophylline dose was 890.0 ± 229.2 mg. We found relatively minor, but in some cases statistically significant, differences in pharmacokinetic parameters between food and fasting administration. When Uniphyl was administered with food, bioavailability was increased by 10% ( p < 0.01), the time of maximum concentration occurred 3 hours later ( p < 0.01), and the minimum or “trough” theophylline concentration was 0.7 mg/L greater ( p < 0.01), as compared to administration while patients were fasting. There was no evidence of “dose dumping” after either food or fasting administration of Uniphyl, and there was no significant difference in the maximum theophylline concentration attained between the two dosing conditions. There was no evidence of a difference in therapeutic efficacy between the two dosing conditions. All patients tolerated the drug well throughout the trial.

Safety and efficacy of once-daily uniphyl tablets compared with twice-daily theo-dur tablets in elderly patients with chronic airflow obstruction

Oxygen desaturation and subclinical coronary artery disease may predispose older patients with chronic airflow obstruction to cardiac arrhythmias, especially when high concentrations of theophylline are present in the blood. To assess the safety and efficacy of Uniphyl tablets, an oral theophylline preparation formulated for once-daily dosing, in elderly patients with chronic airflow obstruction, we conducted a randomized, three-phase, double-blind crossover study comparing evening dosing with Uniphyl tablets, Theo-Dur tablets administered twice daily, and placebo. The patients in the study were scheduled to receive each treatment for two weeks. Each day, symptoms, side effects, peak expiratory flow rates, and use of metered-dose inhalers were recorded. Near the end of each phase, serum theophylline concentrations were measured every two hours between 8:00 A.M. and 8:00 P.M. on two consecutive days. The patients underwent ambulatory Holter monitoring during the final 48 hours of each phase. Twelve patients completed the active-drug phases of the study, but seven of the 12 were removed from the placebo phase because of increasing symptom severity. The difference between the number of patients completing the active-drug and placebo phases was statistically significant (p < 0.001). Treatment with Uniphyl tablets resulted in a significantly (p < 0.05) greater increase in peak expiratory flow rate than Theo-Dur tablet therapy, and both active drugs increased peak expiratory flow rate more than placebo. Circadian variation in peak expiratory flow rate was seen during the placebo and Theo-Dur tablet phases but not during the Uniphyl tablet phase. Symptoms and side effects were similar during the two active-drug phases. Cardiac ectopy was observed in most of the patients, but it was not significantly greater during the theophylline phases than during the placebo phase. Furthermore, ectopic activity was not directly related to the times of maximal serum theophylline concentration.

Is a uniform round-the-clock theophylline blood level necessary for optimal asthma therapy in the adolescent patient?

Twenty-one patients, 12 to 18 years of age, with nocturnal asthma controlled with sustained-release theophylline administered twice daily, were enrolled in a 10-week, double-blind, two-way crossover study that compared Theo-Dur tablets administered twice daily with an equivalent daily dose of Uniphyl tablets administered once daily at bedtime. Seventeen patients completed the study. The mean morning theophylline serum level obtained with Uniphyl tablets was significantly higher than that obtained with Theo-Dur tablets (13.1 versus 9.6 μg/ml, p = 0.02). The mean evening serum level was significantly lower with Uniphyl tablets (6.3 versus 10.1 μg/ml, p = 0.003). Despite these differences in serum concentrations, morning and evening pulmonary function test values (forced expiratory volume in one second and peak expiratory flow rate) and symptom scores were nearly identical for the two preparations, as was the supplemental use of aerosol bronchodilators. Once-daily dosing with Uniphyl tablets may benefit adolescent patients with nocturnal asthma by increasing compliance and providing better asthma control. In addition, the lower daytime theophylline levels produced by this preparation may also reduce long-term adverse effects on behavior and cognition.

Multicenter comparison of once-daily Uniphyl tablets administered in the morning or evening with baseline twice-daily theophylline therapy in patients with nocturnal asthma

Ninety-six patients with reversible airways disease and a history of nocturnal asthma completed a four-week open-label study that compared the effectiveness of Uniphyl tablets (The Purdue Frederick Company, Norwalk, Connecticut) administered once daily in the morning or the evening with twice-daily baseline theophylline therapy. All patients transferred easily from their previous twice-daily theophylline regimen to once-daily Uniphyl therapy. Predose serum theophylline levels and pulmonary function values were similar for the twice-daily and once-daily theophylline regimens. However, both the morning and evening once-daily Uniphyl regimens were judged by the investigators to control the asthmatic symptoms of more patients than did the prestudy twice-daily theophylline. In addition, patient acceptance of the two once-daily Uniphyl regimens was significantly (p <0.01) greater than that of the previous twice-daily theophylline therapy. During the fourth week of the study, the evening Uniphyl dosing schedule resulted in significantly (p <0.01) higher home-monitored morning peak expiratory flow rates and fewer nighttime awakenings than the prestudy twice-daily theophylline regimen. The morning regimen was not associated with such an improvement. The results of the study suggest that a once-daily evening dosage regimen with Uniphyl tablets provides greater control of nocturnal asthma.

Review of the North American experience with evening administration of uniphyl tablets, a once-daily theophylline preparation, in the treatment of nocturnal asthma

Increasing awareness of the exaggerated circadian rhythm in bronchomotor tone that causes most asthmatic patients to have increased respiratory symptoms in the early morning has resulted in a search for dosing strategies that will provide maximal bronchodilatory activity at the time of reduced bronchial patency. The purpose of this paper is to review briefly the published data on the North American experience with evening administration of the once-daily theophylline preparation, Uniphyl tablets. An increasing body of data demonstrates that this regimen produces peak concentrations of theophylline in the blood during the early morning hours, the time of maximal benefit for patients with nocturnal asthma. These data also show that once-daily Uniphyl administered in the evening is superior to both a once-daily morning Uniphyl schedule and to a conventional twice-daily sustained-release theophylline preparation in reducing early morning bronchoconstriction and associated symptoms.

Uniphyl tablets in asthmatic pediatric patients

Uniphyl tablets in asthmatic pediatric patients

Improved control of asthma in the office setting: A large-scale study of once-daily evening doses of theophylline

A large-scale, multi-investigator open evaluation compared a once-daily regimen of controlled-release theophylline (Uniphyl tablets) with previous twice- or thrice-daily methylxanthine regimens. Three hundred asthmatic patients, 78 percent prone to nocturnal episodes during prior therapy, completed the investigation. Eighty-two percent of the patients were treated for moderate or severe disease. After a one-week evaluation of baseline theophylline therapy (with adjunctive medication), the patients substituted evening doses of the once-daily drug in approximate milligram-for-milligram equivalent doses. Concomitant medications were allowed as before. Nighttime and morning asthma control improved significantly without deterioration in the evening, and without increased side effects. Once-daily therapy resulted in markedly fewer night awakenings involving inhaler use (p <0.01), and near 60 percent reductions in the number of patients with nighttime or early morning exacerbations (p <0.01). Control of morning chest tightness, wheeze, and dyspnea improved significantly (p <0.01), and patients' as well as investigators' global evaluations favored once-daily treatment (p <0.01). Morning peak expiratory flow rates, improved both at home (p <0.01) and at the office (p = 0.05). The forced expiratory volume in one second at the office increased modestly in the entire group. It is concluded that Uniphyl is effective and well tolerated when administered in once-daily evening doses.

Circadian variations in chronic asthma and chronic obstructive pulmonary disease

Patients with airway obstruction of all types show circadian variation of airflow. This article reviews the results of studies that suggest both possible mechanisms for this phenomenon and strategies for its treatment. The strategies discussed include the use of sustained-release beta-agonists and a once-a-day theophylline preparation, Uniphyl tablets, that is especially effective in asthmatic patients when administered in the evening. Also presented is a summary of future directions in the planning and implementation of individualized therapeutic strategies for patients with advanced chronic obstructive airways disease.

Once-daily uniphyl tablets versus twice-daily theo-dur tablets in the treatment of nocturnal asthma

Once-daily uniphyl tablets versus twice-daily theo-dur tablets in the treatment of nocturnal asthma

Comparison of Uniphyl tablets and inhaled albuterol as maintenance therapy in asthmatic adults

A new dosage regimen of orally administered acyclovir, 800 mg twice daily for five days, for the treatment of recurrent genital herpes was compared with the standard dosage of 200 mg given five times per day. A double-blind study of 157 patients was used to evaluate the safety and efficacy of both regimens. The new regimen was well tolerated, more convenient, and as effective as the standard dosage. In male patients, the new regimen may be more effective than the standard regimen of 200 mg given five times per day to treat lesions that are already present.

The Contin delivery system: Dosing considerations

The combination of hydrated cellulose with higher aliphatic alcohol forms the basis of the Contin delivery system, used in the development of tablet forms of sustained-release aminophylline, theophylline, morphine, and other drugs. Extensive clinical and pharmacokinetic evaluation of Uniphyl (anhydrous theophylline) tablets, 400 mg, shows that once-daily morning dosing is at least equivalent to twice-daily administration of theophylline. Ingestion of the once-daily product with a high-calorie-high-fat meal in volunteers increased the absorption of theophylline without accompanying “dose-dumping.” Extensive pharmacokinetic evaluation in patients with food intake not controlled has yielded bioavailability comparable to that of twice-daily theophylline. Ongoing research suggests that evening administration of Uniphyl tablets may represent a rational dosing schedule for patients with asthma who often exhibit increased bronchoconstriction in the morning. In these studies patients demonstrate improved pulmonary function in the morning compared with use of twice-daily theophylline when once-daily Uniphyl is administered in the evening. Thus, evening administration of once-daily theophylline may block the morning dip in lung function commonly seen.

Uniphyl tablets at bedtime versus Theo-Dur twice daily in nocturnal asthma

Uniphyl tablets at bedtime versus Theo-Dur twice daily in nocturnal asthma