Pharmacokinetics of theophylline and bioavailability of a sustained release theophylline preparation in patients with cystic fibrosis.

The elimination of theophylline after intravenous aminophylline bolus and the absorption of a sustained-release oral theophylline preparation (Theo-Dur) were studied in ten patients with cystic fibrosis (C.F.). Each patient received an I.V. bolus of aminophylline equivalent to 4 mg/kg anhydrous theophylline and 10 plasma theophylline levels were obtained over the following eight hours. Elimination half life (T1/2), total body clearance (Cl), volume of distribution (Vd) and area under the concentration curve (AUCiv) were determined. Forty-eight hours later each patient received an oral dose of sustained release theophylline equivalent to 7.47-11.42 mg/kg anhydrous theophylline and 13 plasma theophylline concentrations were measured over 24 hours. Area under the concentration curve (AUCpo) and fractional absorption (F) of the sustained release preparation were determined. Mean values (+/- S.D.) were T1/2 = 4.45 +/- 1.58 hrs, Vd = 505.8 +/- 40.7 ml/kg, Cl = 87.9 +/- 31.6 ml/kg/hr, F = 0.86 +/- 0.26. One patient did not develop detectable plasma theophylline levels until 20 hours after receiving the sustained release product, but rapidly absorbed 96% of orally administered theophylline elixir. While we could demonstrate no consistent abnormality of theophylline distribution or elimination in cystic fibrosis patients, large interindividual differences in elimination may exist. In addition, some C.F. patients may have impaired or delayed absorption of sustained release theophylline preparations.