Metabolic Correlates of Theophylline Therapy: A Concentration-Related Phenomenon

Abstract

OBJECTIVE:

To determine the relationship of serum theophylline concentration with electrolyte and glucose abnormalities across a broad range of theophylline concentrations.

DESIGN:

Retrospective review of a computerized laboratory database between June 1, 1984 and June 1, 1986.

SETTING:

A midwestern university medical center.

PATIENTS:

Eight hundred sixty-nine patients with serum theophylline concentrations of >5.5 μmol/L and a random unmatched sample (control group) of 350 in- and outpatient adults and children with no history of reactive airways disease or theophylline exposure.

RESULTS:

Patients with measurable theophylline had a higher risk of hypokalemia, hyponatremia, hyperglycemia, hypophosphatemia, and hypomagnesemia compared with the unexposed control group. Unadjusted odds ratios (OR) were: (1) hypokalemia OR=4.2 (95 percent CI 2.2 to 7.9); (2) hyponatremia OR=5.4 (95 percent CI 2.0 to 12.9); (3) hypomagnesemia OR=1.6 (95 percent CI 1.0 to 2.5); (4) hyperglycemia OR=2.3 (95 percent CI 1.7 to 3.0); and (5) hypophosphatemia OR=2.7 (95 percent CI 1.2 to 5.3). A linear concentration—response relationship was documented between serum theophylline concentration and all metabolic disturbances.

conclusions:

Measurable theophylline was associated with increased risk for glucose and electrolyte abnormalities in a concentration-related fashion across a broad range of theophylline concentrations from 5.5 to ≥110 μmol/L.