Relationships between pharmacokinetics and nonpulmonary pharmacodynamic effects of theophylline.

Concentration-effect relationships between oral theophylline and its nonpulmonary pharmacodynamic effects were examined in a double-blind, randomized, two-way crossover study in which 10 healthy subjects received a single dose of 500 mg ordinary-release theophylline or placebo. Mean plasma theophylline concentrations rose to 16.1 mg.L-1 at 1 hour and 16.8 mg.L-1 at 2 hours. Maximum decreases in plasma potassium (0.33 mmol.L-1) and magnesium (0.039 mmol.L-1) and increases in supine (11.1 mm Hg) and standing (8.0 mm Hg) diastolic blood pressure and plasma total cholesterol (0.59 mmol.L-1) occurred after the achievement of peak plasma theophylline concentrations (negative hysteresis). This delay is consistent with the intracellularly mediated effects of theophylline and with compartmental shifts of electrolytes. Discrepancies between the pharmacokinetic profile and pharmacodynamic effects should be borne in mind when assessing the duration of action of a drug.

RCT Entities:   Population Interventions Outcomes