Use of pharmacokinetic profile in evaluating patients with repeatedly low theophylline concentrations

Assessment of individual pharmacokinetics has been helpful in the evaluation of patients with persistently low serum theophylline concentrations and poorly controlled asthma. This paper presents seven cases where pharmacokinetic profiling specifically identified the etiology for low theophylline concentrations. Pharmacokinetic profiles were done following oral or intravenous dosing of theophylline. Serial blood samples drawn over 12 hours were assayed for theophylline concentrations using HPLC. Serum half-life (t1/2), clearance (Cl), volume of distribution (VD) and time-to-peak concentration were determined for each subject. In this series, three patients exhibited rapid theophylline clearance, two had predictable theophylline pharmacokinetics, and two presented with unique pharmacokinetics. These cases illustrate a wide range of pharmacokinetic behavior seen in clinical practice. To evaluate patients with persistently subtherapeutic theophylline concentrations, determination of individual pharmacokinetic profiles should be performed before prescribing high doses of theophylline (greater than 30 mg/kg/day).