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 (T) tissue distribution was studied in 11 premature newborns treated with T for prematurity apnea, who had died from severe pathology. To investigate the pattern of distribution of T, in particular the role of the blood-brain barrier in this period of life, two animal species were employed (rat and guinea pig), differing widely in their postnatal development. T was administered to the animals acutely and chronically and the resulting data were compared to human findings. In human prematures no specific accumulation and a wide variety in tissue concentrations, as in tissue/blood ratios, were observed. In the rat, unlike the guinea pig, brain/blood ratios of T concentration declined as postnatal age rose, suggesting that development of the blood-brain barrier plays a major role.
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PMID:Theophylline distribution in the premature neonate. 731 39

Theophylline may be administered by several routes, but problems are associated with neonatal dosing. The transdermal route may provide a safer and noninvasive method of administration, yet produce therapeutic concentrations in a consistent and reliable manner. To study the feasibility of this in the apnea of prematurity, stable neonates were administered a subtherapeutic transdermal dose for 24 hours in order to assess pharmacokinetics and bioavailability. This was followed with routine intravenous theophylline therapy according to institutional policy. Six of nine neonates had detectable serum theophylline concentrations that increased slowly after patch application. Mean (+/- SD) maximum serum concentration was 2.4 +/- 1.3 micrograms/ml, mean time to maximum serum concentration was 22 +/- 8.2 hours, and mean latency period was 8.0 +/- 4.9 hours. Mean total amount of theophylline delivered to the skin was 18.6 +/- 4.1 mg. Mean fractional absorption at 30 hours was 0.25 +/- 0.12. These data demonstrate that it is possible to produce systemic theophylline concentrations with a transdermal patch in preterm infants sufficient to study pharmacokinetics and bioavailability, and that transdermal delivery of therapeutic doses is technologically feasible.
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PMID:Evaluation of transdermal theophylline pharmacokinetics in neonates. 836 66

1. Theophylline is commonly used in neonatology for the treatment and prophylaxis of apnoea of prematurity, and during ventilator weaning. 2. NONMEM was used to study the population pharmacokinetics of intravenous and oral theophylline from retrospective drug monitoring data in 82 premature neonates, weighing < 1500 g at birth, and < or = 32 weeks gestational age. 3. Clearance (CL), volume of distribution (V), and oral bioavailability (F1) from liquid preparations were modelled alone, and under the influence of demographic and clinical covariates, assuming a 1-compartment model with first-order elimination. 4. The final population models with influential co-variates were as follows: CL (1h-1) = 0.0000123 *body weight (g) + 0.000377 *postnatal age (days); V (1) = 0.000937 *body weight (g); F = 0.918. 5. The CL was lower and V was higher than previously reported for less premature neonates, term babies, and older children. 6. Predictive performance of the population models was evaluated by Bayesian forecasting in a similar, but independent cohort of 30 infants. There was statistically insignificant bias and imprecision between measured and predicted serum theophylline concentrations. 7. Based on the validated population models, recommended maintenance theophylline dosages are provided for infants aged between 2 and 50 days, and weighing 700 to 2000 g.
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PMID:Theophylline population pharmacokinetics from routine monitoring data in very premature infants with apnoea. 886 18

Theophylline alleviates central and obstructive apneas of prematurity, and may improve adult obstructive sleep apnea. One mechanism of action appears to be a stimulatory effect on the motor output to upper airway dilator muscles. The purpose of the present study was to determine whether theophylline might have a second mechanism of action, namely that of improving the force and/or endurance of the pharyngeal dilator musculature. Rat sternohyoid muscle strips were studied in vitro and compared to diaphragm strips. The isometric twitch force and twitch kinetics of neither muscle were altered by theophylline (100 mg/l). Theophylline significantly slowed the rate at which the diaphragm fatigued during intermittent 40-Hz stimulation (p < 0.001). In contrast, theophylline produced no improvement in the fatigue resistance of the sternohyoid muscle. The degree of force potentiation during the early portion of the fatigue protocol was not altered by theophylline for either muscle. These results suggest that the mechanism by which theophylline improves obstructive apnea is unlikely to be due to a beneficial effect on pharyngeal dilator muscle force or endurance.
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PMID:Effects of theophylline on pharyngeal dilator and diaphragm muscle contractile properties. 896 72

Apnea of prematurity is a common problem of the premature infant under 30 weeks gestation. Theophylline and caffeine, two methylxanthines, are widely used to treat this condition. The drugs are equally effective in preventing apnea in the premature infant. Caffeine citrate has many advantages over theophylline, however, including once-a-day dosing, more predictable plasma concentrations, earlier onset of action, and minimal side effects. Caffeine is therefore the initial drug of choice for apnea of prematurity.
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PMID:Theophylline or caffeine: which is best for apnea of prematurity? 1194 72

A retrospective study was undertaken to assess the association between esophageal pH monitoring variables and signs such as regurgitation, vomiting, apnea, bradycardia, and cyanotic episodes attributable to gastroesophageal reflux (GER) in neonates. One hundred thirty-four infants with one or more of the above-described signs underwent 24-hour distal esophageal pH monitoring in the neonatal intensive care unit, and were divided into 2 groups by gestational age. Group 1 (preterm infant group) consisted of infants aged 25 to 36 weeks of gestation ( n = 45) and group 2 (term infant group) consisted of infants aged 37 to 42 weeks gestation ( n = 89). Esophageal pH monitoring variables were compared by gestational age group and within preterm infants by theophylline treatment and, separately, by nasogastric tube using the Mann-Whitney U test. Comparisons of nominal data were made using the chi square test. Logistic regression analysis was used to assess the net effect of each independent variable on the risk of developing GER. The prevalence of GER was not influenced by gestational age. The prevalence of gastrointestinal signs did not differ between groups. Cardiorespiratory signs attributed to GER were more frequent in preterm infants than in term infants. The number of episodes with pH < 4 in 24 hours was greater in the term compared with the preterm infant groups. Logistic regression analysis failed to detect an association between acid GER and gestational age, apnea, bradycardia, cyanotic episodes, vomiting, or regurgitation. Theophylline treatment and the presence of a nasogastric tube did not significantly affect the esophageal pH monitoring variables in preterm infants. Preterm infants have a smaller number of reflux episodes compared with term infants. In addition, treatment with theophylline for apnea of prematurity and the presence of a nasogastric tube in preterm infants did not significantly affect pH-monitoring variables in preterm infants.
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PMID:Esophageal pH study and symptomatology of gastroesophageal reflux in newborn infants. 1501 72


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