Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D06103 (Theophylline)
 2,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Theophylline is administered to preterm infants with pulmonary disease to improve pulmonary function and reduce apneic episodes. Because it potentially mediates both alpha- and beta-receptor-effector mechanisms, we tested the hypothesis that it increases lipolysis, gluconeogenesis from glycerol, and energy expenditure in 16 preterm infants, eight of whom were treated therapeutically with theophylline for apnea of prematurity (T) and eight of whom were controls (C). Mean +/- SD postnatal ages were 4.8 +/- 1.9 wk (T) and 2.4 +/- 0.9 wk (C) (p < 0.01). Corrected gestational ages were 35 +/- 1.6 wk (T) and 34 +/- 0.5 wk (C) (p = NS). Body weights were 1.69 +/- 0.13 kg (T) and 1.70 +/- 0.23 kg (C) (p = NS). All infants were clinically stable, breathing room air, fed enterally, and receiving no diuretics, steroids, or antibiotics. Lipolysis, hepatic glucose production, and gluconeogenesis from glycerol were measured using [2-13C]glycerol and [6,6-3H2] glucose tracers. Body water and energy expenditure were measured by the 2H2(18)O method. Body water volumes were 68.5 +/- 3.4% body weight (T) and 70.2 +/- 3.4% (C) (p = NS), suggesting fat was 10-13% of body weight in both groups. Mean daily energy expenditure was 65 +/- 22 kcal/kg body weight/d (T) versus 59 +/- 5 kcal/kg body weight/d (C) (p = NS). Between 4 and 6 h after a feeding, glucose production rates were 40.5 +/- 4.3 mumol/kg/min (T) and 37.6 +/- 4.8 mumol/kg/min (C) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Energy expenditure, lipolysis, and glucose production in preterm infants treated with theophylline. 128 61

Respiratory diseases are major causes of morbidity and mortality in premature neonates. Theophylline has been utilized as an adjunct in facilitating ventilator weaning and in the management of apnea with or without bradycardia. Patient characteristics associated with improved outcome from theophylline have not been determined. The purpose of this study was to evaluate parameters associated with improved outcome in neonates with respiratory diseases receiving theophylline. The study population consisted of premature neonates that were studied retrospectively. Criteria for entry into the study were (1) less than 40 weeks gestation, (2) a diagnosis of respiratory distress syndrome (RDS), apnea of prematurity, hyaline membrane disease (HMD), or bronchopulmonary dysplasia (BPD), (3) dependence on intermittent mandatory ventilation, (4) failure to wean from the ventilator 24 h or more before the study, or (5) receiving theophylline. In this study, we found no correlations between time to wean from the ventilator and postnatal age at the time theophylline was initiated, 5-min APGAR score, and final theophylline serum concentration before complete weaning from the ventilator. However, there were significant negative correlations between birthweight and gestational age with respect to time to wean from the ventilator. The average theophylline serum concentration before weaning from the ventilator for this population of neonates was approximately 5-10 micrograms/ml, indicating that theophylline is not beneficial as an aid to ventilator weaning at serum concentrations < 10 micrograms/ml.
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PMID:Use of theophylline in neonates as an aid to ventilator weaning. 148 68

The incidence and proposed mechanisms of apnea of infancy and apnea of prematurity are briefly reviewed, and the use of methylxanthines in managing these conditions is discussed. Apnea may result from incomplete neurological development of the infant. A sleep-related defect in respiratory control mechanisms has been proposed. Apnea may be secondary to physiologic abnormalities that cause airway obstruction or to cardiac disease or arrhythmia, seizure disorders, infection, or other disorders. Therapy often includes supportive management. The primary pharmacologic agents used to treat apnea of prematurity are caffeine and theophylline. The metabolism of these drugs differs greatly between newborns and adults and changes rapidly in the first nine months of life; in infants up to 4 1/2 months of age, the half-life of these compounds is prolonged. While only theophylline is approved in the United States for management of apnea, caffeine has several potential advantages. However, no suitable caffeine product is available. The accepted pharmacologic treatment for apnea of prematurity is the use of the methylxanthines theophylline and caffeine. Theophylline has also been used in treating apnea of infancy, although there are fewer data documenting its efficacy for this indication.
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PMID:Management of apnea in infants. 267 Mar 99

Theophylline is an effective respiratory stimulant for apnea of prematurity. In the newborn, theophylline stimulates the central nervous system, particularly the respiratory center, leading to decreased apnea frequency and increased ventilation. Neonates appear to be more sensitive to the cardiovascular effect of theophylline; tachycardia occurs at plasma concentrations of 13 mg/L. Minimal effects on renal and gastrointestinal function are observed at therapeutic doses. Augmentation in oxygen consumption and alteration in glucose homeostasis may occur, even at therapeutic doses. If used appropriately, the drug is safe and effective for the treatment of neonatal apnea.
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PMID:Pharmacologic effects of theophylline in the newborn. 353 58

To determine the effect of phenobarbital sodium therapy and subependymal intraventricular hemorrhage (SEp-IVH) on the theophylline requirement of premature infants suffering with apnea and seizure activity, we compared three groups of patients as follows: group 1, those with apnea of prematurity (ten patients); group 2, those with apnea and SEp-IVH (ten patients); and group 3, those with apnea, SEp-IVH, and seizure activity for which they were receiving phenobarbital therapy (nine patients). Patients in groups 1 and 2 required lower dosages and blood levels of theophylline to control their apnea than did those in group 3, who required higher dosages and blood levels of methylxanthines. Theophylline dosages and blood levels did not significantly differ between groups 1 and 2. In group 3, the theophylline requirement for control of apnea was significantly increased after initiation of phenobarbital therapy. There seems to be a direct correlation between the increased requirement for theophylline and concomitant phenobarbital administration. The data suggest that phenobarbital increases theophylline requirement when treating neonatal apnea.
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PMID:Phenobarbital increases the theophylline requirement of premature infants being treated for apnea. 378 91

The respiratory performance was studied after intraperitoneal administration of the adenosine agonists N6-phenyl-isopropyl-adenosine (PIA) and adenosine-5-ethylcarboxamide to preterm (gestational age 29-30 days) newborn halothane-anesthetized rabbits. Both agonists induced marked hypoventilation and irregular breathing by decreases in the breathing frequency as well as the tidal volume. Expiratory time was markedly prolonged, resulting in a decrease in the respiratory duty cycle (inspiratory time/total cycle duration). Analysis using the occluded-breath technique revealed that the adenosine analogues altered the time setting of the expiratory (inspiratory) neuronal circuits and lowered the inspiratory off-switch level, while inspiratory drive and the bulbopontine setting of the inspiratory phase were unaltered. The ventilatory response to CO2 was blunted after both adenosine analogues studied. Theophylline almost completely reversed the hypoventilation and irregular breathing seen after PIA injection. It is concluded that activation of central nervous adenosine receptors induced a marked respiratory depression in the preterm rabbit. Furthermore, our data imply that an overactivity of central adenosine mechanisms may have a pathophysiological significance for the irregular breathing or apnea of prematurity sometimes seen in the human neonate.
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PMID:Characterization of adenosine-induced respiratory depression in the preterm rabbit. 383 98

Theophylline is commonly used to treat apnea of prematurity. To determine the effectiveness of theophylline with respect to gestational and postnatal age, we conducted a controlled study in 43 premature infants with idiopathic apnea. Three of the 21 treated and eight of the 22 control infants developed respiratory failure. Eight of the 11 infants with respiratory failure had gestational ages of less than 31 weeks and had more than four apneic episodes during the first day of life. In the treated infants without respiratory failure, the number of apneic episodes by 24-hour intervals declined six days earlier than in the control infants. Apnea disappeared, however, at a similar time in both groups. Three treated infants and three control infants had apneic episodes persisting beyond the neonatal period. Patients treated with theophylline did not develop respiratory failure as often as control infants did. However, despite a reduction of apneic episodes, theophylline did not shorten the course of apnea of prematurity.
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PMID:Limitations of theophylline in the treatment of apnea of prematurity. 389 May 20

This study investigated the prolonged effects on state behavior of theophylline administered to infants for apnea of prematurity. There were three groups: Four premature infants who had received theophylline in the preterm period, five premature infants who had not received theophylline, and twenty-eight normal fullterm infants. The Theophylline infants had been off the drug for at least one month prior to the beginning of the study. Sleep-wake states were observed in the home for seven-hour periods when all infants were the same corrected ages: two, three, four and five weeks post-term. Data from the portion of the day that the infants were alone were analysed for this study. The state organization of the Theophylline group differed significantly from those of the other groups. They exhibited more non-alert waking activity, more alert, more drowse or transition, and less active sleep than did the Non-Theophylline and Fullterm infants. The state distributions of the latter two groups did not differ. On the basis of similarities between the results of this study and of a previous animal study, it was concluded that theophylline altered the normal development of state organization in premature infants. These effects persisted long after the drug had cleared the body.
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PMID:Theophylline affects sleep-wake state development in premature infants. 397 97

The concentration of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major metabolites of dopamine and norepinephrine, respectively, were studied in the cerebrospinal fluid (CSF) of 34 newborn infants. No significant difference was found in the levels of MHPG and homovanillic acid between preterm and term infants. Apneic preterm infants had significantly higher levels of MHPG than nonapneic prematures. Theophylline did not change the levels of these metabolites in CSF. There was a progressive rise of MHPG levels in CSF in preterm infants as their postnatal age increased. We suggest that idiopathic apnea of prematurity is not associated with depletion of catecholamine stores in the central nervous system. Theophylline does not seem to relieve apnea by stimulation of the central adrenergic system.
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PMID:Cerebrospinal fluid concentration of biogenic amine metabolites in idiopathic apnea of prematurity. 685 11

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.
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PMID:Pharmacokinetics of theophylline in neonates. 730 9


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