Sustained-Release Theophylline for Treatment of Asthma in Preschool Children

Theophylline in Asthma

“…27 Although the degree of attenuation is relatively small for most of these bronchoconstrictors, theophylline can completely inhibit airway responsiveness to exercise at a serum concentration of у 15 m g per milliliter 22 -a value in the upper half of the range (10 to 20 m g per milliliter) that provides optimal control of chronic asthma. 3,5,28,29 None of these bronchoprotective effects correlate well with the degree of bronchodilation produced by theophylline before the challenge. For substances such as methacholine and histamine that directly stimulate the contraction of bronchial smooth muscle, the bronchoprotection may be effected by direct inhibition of smooth-muscle contraction.…”

“…50 In a crossover study of adults (median age, 51 years), 51 two weeks of salmeterol was more effective than two weeks of theophylline, but only 98 of the 141 patients completed the trial and more than half the patients had serum theophylline concentrations below the range of 10 to 20 m g per milliliter within which efficacy is most likely to be maximal. 3,5,28,29 Although several large trials have reported sustained bronchodilation and clinical efficacy with the long-term use of salmeterol, 50 there is concern about the loss of the drug's bronchoprotective effect after challenge with methacholine, 52 exercise, 53 and allergen inhalation 54 after as little as two weeks. In contrast, attenuation of airway responsiveness to exercise is sustained with theophylline.…”

“…In patients receiving theophylline as monotherapy for chronic asthma, doses providing peak serum concentrations between 10 and 20 m g per milliliter are the most likely to prevent symptoms and decrease the need for rescue therapy. 3,28,29 However, bronchodilatory, antiinflammatory, and immunomodulatory effects of theophylline occur at lower serum concentrations, which may be adequate for some patients.…”

A Clinical and Pharmacokinetic Basis for the Selection and Use of Slow Release Theophylline Products

“…In a crossover design study comparing plain uncoated theophylline tablets taken every 6 hours around-the-clock with a slowly absorbed slow release product given every 12 hours to 35 children with chronic asthma, significantly more days free of wheezing were documented during the slow release regimen, even though the total daily dosage, individualised during both regimens to achieve a peak serum theophylline concentration between 10 and 20 J.Lg/ml, was similar (Tabachnik et aI., 1982). In addition, Simons et al (1982) reported a dramatic increase in the need for inhaled salbutamol, in association with declining theophylline serum concentrations 9 to 12 hours after a dose, in 7 of 10 children taking a slow release product twice daily. Inhaled salbutamol was not required earlier in the dosing interval when the serum concentration averaged 6 J.Lg/ml higher than the trough.…”

The rise and fall of serum theophylline concentration: a comparison of sustained‐release formulations in volunteers with rapid theophylline clearance.

“…Sustained-release formulations delay the Correspondence: Dr J. C. Mucklow, Department of Clinical Pharmacology, City General Hospital, Stoke-onTrent, ST4 6QG appearance, and reduce the size, of peak concentrations; twice-daily dosing is usually adequate, but the acceptability of the formulation still depends on the extent to which theophylline absorption is retarded. In subjects whose theophylline clearance is especially high, even a sustained-release formulation may result in excessive oscillation of drug concentration between doses, and the dose interval will have to be reduced (Simons et al, 1982;Weinberger et al, 1981); the use of such individuals for the comparative evaluation of sustained-release formulations is likely to exaggerate any differences between preparations, and this may assist product selection in children and in adults who smoke.…”