Alterations in theophylline protein binding in acutely ill patients with COPD

We investigated the role of decreased theophylline protein binding as a possible explanation for observed decreases in total theophylline concentrations (TC) in acutely-ill patients (AIP). Multiple blood samples were obtained from nine AIP with underlying chronic obstructive pulmonary disease (COPD) and from 13 stable COPD patients. The mean albumin concentration +/- SD was 2.7 +/- .61 mg/dl in the AIP vs 4.0 +/- 0.52 mg/dl in the stable COPD patients (p less than 0.005). Total (TC) and unbound theophylline concentrations (UTC) were determined. Theophylline protein binding was assessed at room temperature by centrifugal ultrafiltration of the patients' sera. The TC was 13.7 +/- 4.8 micrograms/ml in the stable COPD patients vs 11.8 +/- 4.1 micrograms/ml in the AIP although the mean dose was larger (17.21 +/- 5.41 vs 10.7 +/- 4.09 mg/kg/day of theophylline) in the AIP (p less than 0.005). There was no difference in UTC between the two groups (7.4 +/- 2.5 micrograms/ml and 8.1 +/- 2.6 micrograms/ml); however, the unbound fraction was higher in the AIP (p less than 0.005). We conclude that theophylline protein binding appears altered in AIP and that the altered binding relates predominantly to the severity of the clinical illness.