Theophylline dosing interval

If the asthma attack is relieved, the clinician might want to maintain this plasma level using oral theophylline, which might be given every 12 hours using an extended-release formulation to approximate a continuous intravenous infusion. According to Table 3-1, Fora is 0.96. When the dosing interval is 12 hours, the size of each maintenance dose would be ... 

FIGURE 3-4 Relationship between dosing interval and plasma concentrations of the antiasthmatic drug theophylline. A constant intravenous infusion [shown by the smoothly rising line] yields a desired plasma level of 10 mg/L. The same average plasma concentration is achieved when a dose of 224 mg is taken every 8 hours, or a dose of 672 mg every 24 hours. However, note the fluctuations in plasma concentration seen when doses are taken at specific hourly intervals. 

Theophylline administered in liquids or uncoated tablets is absorbed rapidly and completely. In the absence of food, solutions or uncoated tablets of theophylline produce maximal concentrations in plasma within 2 hours and maximal plasma concentrations are achieved within I hour. Numerous sustained-release preparations of theophylline are available, designed for dosing intervals of 8, 12, or 24 hours. There is marked interpatient variability in the rate and extent of absorption, and especially in the effect of food and time of administration on these parameters. Thus, it is necessary to avoid substituting one apparently similar product for another. 

Intrasubject variability in the extent of absorption has also been described. The net result is large fluctuations in serum concentrations in some, but not aU dosing intervals, which may cause major problems in terms of interpretation of measured serum concentrations. - Similarly, diurnal variations in theophylline absorption with slower rates at night have to be taken into account. ... 

The steady-state peak serum theophylline concentration is a function of dose and dosing interval that are controlled by the respective health-care professional, and theophylline absorption rate and clearance determined by the dosage form used and the individual patient treated. Because rate and completeness of absorption vary for different formulations, only products with complete absorption should be preferred, especially if switching between formulations. The formulation selected should be capable of maintaining stable serum concentrations when taken no more often than twice daily. 

For the aminophylline dosage regimen of 150 mg every 4h (i.e. 118.5 mg theophylline every 4 h), one would expect greater accumulation of drug since dosing interval (t) is smaller. The dmg accumulation can be determined by employing same methods. For example. 

Initial dose 16 mg/kg per 24 hours or 400 mg per 24 hours, whichever is less, of anhydrous theophylline in divided doses at 6- or 8-hour intervals. 

Theophylline improves long-term control of asthma when taken as the sole maintenance treatment or when added to inhaled corticosteroids. It is inexpensive, and it can be taken orally. Its use, however, also requires occasional measurement of plasma levels it often causes unpleasant minor side effects (especially insomnia) and accidental or intentional overdose can result in severe toxicity or death. For oral therapy with the prompt-release formulation, the typical dose is 3-4 mg/kg of theophylline every 6 hours. Changes in dosage result in a new steady-state concentration of theophylline in 1-2 days, so the dosage may be increased at intervals of 2-3 days until therapeutic plasma concentrations are achieved (10-20 mg/L) or until adverse effects develop. 

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