Robert L. Mayock

Factors influencing theophylline serum protein binding.

We studied a number of influences on theophylline binding to serum proteins using equilibrium dialysis (37°), a modified Krebs‐Ringer bicarbonate buffer (pH 7.4), and 8‐14C‐theophylline with unlabeled theophylline (30 μg/ml) added to sera from healthy subjects. Theophylline protein binding rose by 18.6% as pH rose from 7.0 to 7.8 (percent theophylline bound = 28.2 ±4.3 at pH 7.0 and 46.8 ± 4.9 at pH 7.8, n = 5). Average theophylline binding to the proteins at 37° in serum samples from 10 normal adults was 39.3 ±3.44%, which is 8.9% lower than the average of 48.2 ± 3.74% for the same samples at 26°. Theophylline binding was 6.1% higher with 0.1 mole/l phosphate buffer, pH 7.4, than with a modified Krebs‐Ringer bicarbonate buffer, pH 7.4. Of the 19 drugs and metabolites tested for competition with theophylline for binding sites on serum proteins, 10 induced decreases in binding ranging from 6.8% in the case of furosemide to 18.3% for sodium salicylate. The latter was the only drug that induced a decrease in theophylline binding at concentrations that would be achieved in the therapy of some patients (i.e., patients on long‐term salicylate therapy). All the other drugs that decreased theophylline binding did so at much greater concentrations than their usual therapeutic levels. The mean ± SD of theophylline bound in 51 fresh serum samples from healthy adults was 48.6 ± 10.2%; the pH of these specimens varied from 7.6 to 8.7. After adjusting pH to 7.4, theophylline binding was lowered to 37.6 ± 4.5% and intersubject variability decreased. We recommend that the pH of serum specimens be adjusted to 7.4, or to the original pH of the blood specimen if it differs significantly from 7.4 (i.e., in acidotic or alkalotic patients). The wide range of reported values for theophylline binding to serum proteins in normal and asthmatic adults at least partly results from differences in the conditions used for the separation of free from bound drug.

Chronic eosinophilic pneumonia followed by polyarteritis nodosa complicating the course of bronchial asthma: Report of a case☆

The syndrome of pulmonary infiltrates with eosinophilia (PIE) occurs rarely in the asthmatic patient. An unusual case is presented in which progressive bronchoconstriction and exaggerated blood eosinophilia preceded the recognition of two seemingly unrelated diseases, each of which can independently result in hypereosinophilia and the PIE syndrome. In the male patient studied, the first illness, biopsy-proved chronic eosinophilic pneumonia, was responsive to corticosteroid therapy. Four uneventful years later, polyarteritis nodosa with eventual pulmonary involvement developed. A careful search for specific underlying pulmonary and systemic disease is in order when hypereosinophilia occurs in the clinically unstable asthmatic patient.