Theophylline Update: Current Controversies

Hill, Malcolm; Szefler, Stanley J.

doi:10.1055/s-2007-1012677

Cited by 5 publications

(1 citation statement)

References 38 publications

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“…It promotes diuresis, and stimulates the release of catecholamines from the adrenal medulla. Theophylline also enhances secretion of gastric acidP] In addition, an anti-inflammatory effect, as a result of inhibition of histamine release from mast cells, has been ascribed to theophylline.l 4 ] Results from in vitro studies suggest that the pharmacological effect of theophylline is not only © Adis International Limited. All rights reserved.…”

Section: Discussionmentioning

confidence: 99%

Influence of Endogenous and Exogenous Effectors on the Pharmacokinetics of Theophylline

Tröger

Meyer

1995

Clinical Pharmacokinetics

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Theophylline has been widely used as a bronchodilatory drug for the treatment of neonatal apnoea in premature newborns and patients with obstructive airways disease. The development of analytical equipment and procedures to determine the systemic concentration of theophylline renders it possible to improve the effectiveness of theophylline therapy and reduce the incidence of toxic and adverse effects. Since the beginning of the 1970s, endogenous and exogenous factors (e.g. age, blood pH, concomitant diseases and drug therapy, meal preparation procedure, nutritional habits, pregnancy, gender, smoking and, to a lesser extent, biorhythms), influencing nearly all parameters of theophylline pharmacokinetics have been described. Drug absorption depends on galenic formulation, drug delivery, nutritional habits and the chemical derivatives used. The mean plasma protein binding rates depend on the method of plasma protein determination: acidic blood pH values and advanced age may result in reduced plasma proteins. The volume of distribution depends primarily on age; it is 2-fold greater in newborns than in adults. Furthermore, changes in blood pH values, the plasma protein content and the administration of concomitant drugs may vary this parameter. Biotransformation is the most clinically important pharmacokinetic parameter. Hepatic metabolism accounts for 90% of the metabolism of theophylline. Essentially, 2 microsomal isoenzymes of the cytochrome P450 system appear to be responsible for the N-methylation and 8-hydroxylation of the drug. Age and concomitant disease are the major endogenous effectors influencing biotransformation of theophylline, whereas biorhythms, gender and pregnancy are of lesser importance. Exogenous factors, such as concomitantly administered drugs, smoking and nutritional factors, affect biotransformation by inducing or inhibiting the metabolising enzymes. Because of intra- and interindividual variability in the pharmacokinetics of theophylline, which may be increased by the presence of endogenous and/or exogenous effectors, it is necessary to supervise theophylline therapy by therapeutic drug monitoring if target concentrations are to be achieved.

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Section: Discussionmentioning

confidence: 99%