Plasma theophylline levels after sustained‐release aminophylline

Abstract

Healthy adult subjects were given oral sustained-release (SR) aminophylline tablets 225 mg 12-hourly (n = 12) or 450 mg 12-hourly (n = 6) for 5 doses, and all were given aminophylline 225 mg intravenously on a separate occasion to determine individual kinetic parameters. The mean plasma theophylline half-life ( 1 1/2) from the intravenous study was 5.8 hr (SD +/- 1.9). During the 12 hr after the fifth dose of SR aminophylline, the maximum and minimum mean (SD) plasma theophylline levels were 9.7 (3.2) mug/ml and 4.9 (2.0) mug/ml for the 225-mg dose, and 21.1 (2.2) mug/ml and 11.6 (4.4) mug/ml for the 450-mg dose. Side effects were generally mild in the low-dose study, but in the high-dose study 3 subjects reported headache and 1 was withdrawn after 3 doses. Two subjects also noted nausea, and 3 reported insomnia and anxiety in the high-dose study. It was concluded that there was a considerable range of doses needed to achieve adequate plasma levels, and that the formulation studied was capable of producing reasonably stable and satisfactory plasma theophylline levels once individual dose requirements had been established.

A single-dose comparison of four slow-release theophylline preparations in normal subjects

“…When administered in standard tablet formulations, theophylline has a plasma elimination half-life of about 6 hr (Trembath and Boobis, 1979) and therefore requires 6or 8-hourly administration to maintain adequate therapeutic plasma concentrations (6-12 ,Lmol/l). Several slow release preparations have therefore been introduced which have been claimed by their manufacturers to provide rapid and sustained plasma levels for longer durations, so improving compliance and minimizing the plasma peaks and related adverse effects commonly encountered with conventional theophylline formulations.…”

A Study on the Effects of a Combined Frusemide and Controlled Release Potassium Tablet (Diumide‐K Continus® tablets) on Gastrointestinal Mucosa

“…One such example of the latter is Diumide‐K Continus® tablets which is commonly prescribed. The KCl in this tablet is incorporated in a controlled release system which has been shown to produce predictable and reliable blood levels when used with other drugs such as aminophyliine, 11 theophylline 12 and morphine 13 . Therefore, it was felt ethically necessary to investigate the effects of this tablet on the gastric, duodenal and oesophageal mucosa in healthy volunteers.…”

Oral sustained‐release aminophylline in medical inpatients: factors related to toxicity and plasma theophylline concentrations.

“…Oral preparations yielding plasma theophylline concentrations reliably between 5-15 jg/ml have therefore been sought. Sustained-release tablets have a potential advantage (Hendeles, Weinberger & Johnson, 1978) and have appeared satisfactory in preliminary testing (Jenne et al, 1972;Boroda, Miller, Leslie, Nicol & Thomson, 1973;Mitenko & Ogilvie, 1974;Sims, Kelly & Shanks, 1976;Trembath, Boobis & Richens, 1979). However, plasma theophylline concentrations vary widely between patients given the same dose of aminophylline (Jenne et al, 1972).…”

“…Despite knowledge of these factors, and even with monitoring of plasma theophylline concentrations (Hendeles et al, 1978), there remains a considerable element of trial and error when prescribing oral theophylline derivatives (Van Arsdel & Paul, 1977;Ogilvie, 1978a). We have studied prospectively the use of a controlled-release aminophylline tablet, Phyllocontin ContinusS (Boroda et al, 1973;Trembath et al, 1979) in medical inpatients. The study was discontinued because toxicity was encountered much more frequently, and at lower dosage, than was anticipated from published work.…”