Theophylline therapeutic range

The therapeutic range of theophylline blood levels is 10 to 20 p,g/mL. Levels greater than 20 pig/mL may cause toxicity. In some patients, toxicity may occur with levels between 15 and 20 pg/mL. Toxicity is more likely to occur in patients requiring high doses or during prolonged dierapy. 

Dose adjustments should generally be made based on trough serum concentration results. A conservative therapeutic range of 8 to 15 mcg/mL is often targeted, especially in elderly patients, to minimize the likelihood of toxicity. Once a dose is established, concentrations should be monitored once or twice a year unless the disease worsens, medications that interfere with theophylline metabolism are added, or toxicity is suspected. 

Jl, J4, T6). Little benefit can be demonstrated at lower plasma levels. In one study adjustment of dosage to maintain steady-state plasma theophylline levels within a recommended optimum therapeutic range of 10-20 /ig/ml led to improved therapeutic control (J4). To achieve this a more than 8-fold difference in the daily dose was necessary (J4), due to variations between one subject and another in the rate of metabolic degradation of theophylline. 

THEOPHYLLINE Individualize dosage. Base dosage adjustments on clinical response and improvement in pulmonary function. Monitor serum levels to maintain levels in the therapeutic range of 10 to 20 mcg/mL. 

Methylxanthines have a number of other effects, including effects on smooth muscles and the cardiovascular system. The most notable effect on smooth muscles is relaxing the bronchi of the lungs. Theophylline is prescribed to treat mild forms of asthma. While both caffeine and theophylline will relax the bronchial smooth muscles, theophylline is used therapeutically because of its longer half-life. This allows the drug to stay in the therapeutic range longer. 

This xanthine derivative is an only a modest bron-chodilator in COPD, and because of its narrow therapeutic range, frequently seen adverse effect and drug interactions, it is becoming less frequently used, some patients experience side effects even within the therapeutic range. The non-bronchodilator effects of theophylline such as systemic and pulmonary vascular dilatation, central nervous system stimulation, improvement of the strength and effectiveness of respiratory muscles and possibly anti-inflammatory effects are of disputed clinical significance at usual therapeutic levels. 

One commonly administered drug in these infants is theophylline which is used in the treatment of apnoea. In order to examine the feasibility of delivering this drug, a simple gel formulation containing 15J theophylline sodium glycinate in 5% hydroxymethyl cellulose was prepared [JJ2,]. This formulation was chosen using the kinetic model such that the input rate of theophylline produced plasma levels in the therapeutic range 4 to 12 mg/1. Thirteen infants were studied and in all but two cases therapeutic levels... 

FIGURE 18.16 Theophylline pharmacodynamics in patients with asthma. Effect, which was measured as improvement in forced expiratory volume in 1 second (FEVI), is related to the serum drug level in six patients, who were studied after placebo and tliree incremental doses of theophylline. An Emax model is fit to the concentration-effect data. Based on this analysis, a therapeutic range of 10-20 pg/mL was proposed (shaded area). (Adapted from data published by Mitenko PA, Ogilvie RI. N Engl J Med 1973 289 600-3.)... 

Because theophylline has a relatively narrow therapeutic index, it would be desirable to determine a dose at which the maximal and minimal concentrations at steady state will be within the therapeutic concentration range (5-15mg/L). Therefore, the 280 mg bid dose regimen is convenient and adequate to achieve Cmax and Cmin within the therapeutic range. 

Most medications have shorter half-lives in children than in adults, and therefore children may need sustained-release products to maintain serum concentrations in the therapeutic range. For example, a sustained-release theophylline product may be needed for a child with asthma. It may need to be administered every 8h to the child as compared to every 12 h for a healthy, non-smoking adult to maintain therapeutic serum concentrations. When choosing a sustained-release theophylline preparation for a child, it must be remembered that because of differences in release properties, theophylline sustained-release products are not interchangeable. A product selected for the pediatric asthma patient should be reliably absorbed with a minimal serum concentration variation and not a preparation that has exhibited a difference in bioavailability when administered with or without food.[ > - ]... 

Norfloxacin and ciprofloxacin decrease the systemic clearance of theophylline to an extent that could be of clinical significance (Prince et al.r 1989). The effect of the interaction can be avoided by adjusting the dosage rate of theophylline in accordance with the decreased clearance so that steady-state plasma theophylline concentrations remain within the therapeutic range (6-16 pig/mL). 

As with erythromycin, drug interactions are extremely important with clarithromycin. Because clarithromycin inhibits the hepatic cytochrome P-450 system, it may result in increased levels of multiple medications metabolized by the liver [19]. Clarithromycin appeared to increase the mean steady-state plasma theophylline concentration and AUC from 15.6 p.g/ml and 249 pg hr/ml, respectively, in the absence of clarithromycin, to 18.4 pg/ml and 291 pg hr/ml in the presence of clarithromycin p< 0.001 for both concentration and AUC). Although a modest increase was seen in the plasma theophylline concentration, the concentration remained within the therapeutic range, and concurrent administration of clarithromycin and theophylline was safe and well tolerated [121]. Although the magnitude of elevation in theophylline was small, caution should be used when... 

A serum theophylline level between 10 and 20 pg/mL indicates the medication is within the therapeutic range, but it is not the best indicator of the client s control of the signs or symptoms. 

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