Prediction of serum-theophylline level using the disease factor product a pilot study - abstract

In this pilot study, we examined the performance of a population-based pharmacokinetic model designed to predict serum theophylline levels in patients with compromised pulmonary function. Ten patients were followed prospectively and the measured steady-state theophylline levels were compared with the predicted levels, that were calculated with formulae based on the disease factor product (DFP). DFP is the combined product of all factors that are known to influence theophylline clearance. In this way, an individualized theophylline clearance could be calculated and a prediction for the steady-state serum level of theophylline could be made. We found no significant difference between the predicted and measured theophylline levels, regardless of whether DFP was calculated with all present factor (approach 1) or with only the largest enhancing and the largest inhibiting factors (approach 2) present. For individual patients the best correlation (R = 0.68) between measured and predicted levels was found with approach 1. Therefore, there is evidence from this pilot study, that the pharmacokinetic model performs in a clinically acceptable manner and could be used to individualize theophyline therapy and adjust the dosage regimen to changes in patients' disease factors(AU)

Malnutrition and theophylline clearance in the elderly

Thirteen elderly, clinically malnourshed (mean age 75.7) were studied for theophylline clearance before and after treatment for malnutrition. Theophylline half-life and clearance values were within normally reported values though the mean clearance value was greater (p<0.001) than that in a control group. Following treatment for malnutrition the clearance increased by 36 percent (p<0.05). This is an indication that the requirements of geriatric patients may need revision upon the nutritional rehabilitation which is expected following admission to appropriate facilities (AU)

Chronic obstructive lung disease: a role for theophylline?

Asthma, chronic obstructive bronchitis, and emphysema represent different forms of chronic obstructive pulmonary disease (COPD). Because they have different causes and are based on different pathophysiology, it is reasonable to suspect they may respond differently to treatment. In particular, bronchodilators, such as theophylline, which are purported to act by preventing the spasm of bronchial smooth muscle, should work in asthma but not in chronic bronchitis or emphysema. However, theophylline and other bronchodilators do improve breathing in all three forms of COPD, although to different degrees. Theophylline's effectiveness in chronic bronchitis and emphysema is attributed, in part, to the observation that these forms of COPD commonly have a reversible component (bronchospastic). Furthermore, it is now known that theophylline's mechanism of action includes a strengthening of the diaphragm and other muscles of respiration. These additional mechanisms may explain theophylline's effectiveness in those forms of COPD that lack a bronchospastic component. (AU)

Theophylline clearance in malnourished elderly subjects - abstract

Many factors, including age and nutritional status, can affect drug metabolic rates. This study was designed to assess the metabolising capacity for the anti-asthmatic drug, theophylline, in malnourished elderly subjects before and after nutritional rehabilitation. Thirteen elderly, clinically malnourished subjects (aged 65-88 yrs.) were studied three to four days after admission to hospital for social reasons, and again after ten days of re-feeding with a high calorie, high protein diet. Theophylline half-life (T«) and clearance (CI) were determined from blood samples taken between 3 and 24 hours after a dose of 3.5 mg/kg. Malnutrition was assessed clinically and by serum albumin, haemoglobin and thyroid binding pre-albumin (TBPA). Serum albumin and TBPA were positively correlated and both increased after re-feeding. Theophylline Tu« and Cl values were within reported ranges. Half-lives were the same as those of healthy adult controls, but clearances were greater. Cigarette smokers were among the slowest, suggesting some other factor of malnutrition or acute hospitalisation may accelerate metabolism. On re-feeding, clearances increased by 37 percent, showing a great capacity of the elderly to respond to dietary supplementation; the subjects who were most malnourished had the lowest Cl rates and responded with the greates increase. These results have important implications for the selection of drug dose regimes for elderly hospitalised patients as the drug requirements may changed considerably during rehabilitation (AU)