Theophylline clearance in patients with severe chronic obstructive pulmonary disease receiving supplemental oxygen and the effect of acute hypoxemia.

Abstract

The effect of hypoxemia on the disposition of theophylline was examined in 10 stable patients with chronic obstructive pulmonary disease (COPD) receiving chronic theophylline and supplemental home oxygen therapy. Pharmacokinetics after intravenous theophylline were estimated on the second day of supplemental oxygen (PaO2, 69 +/- 4 mmHg; mean +/- SEM) and on the second day of room air breathing (PaO2, 43 +/- 3) using a randomized cross-over design. On each occasion stable isotope-enriched theophylline (10 mg, m/z 183) was administered intravenously along with the regular oral dose of theophylline (m/z 180). Concentrations of both forms of theophylline in plasma samples obtained over 24 h were measured using mass spectrometry. Theophylline clearance during oxygen therapy (0.048 +/- 0.005 L/h/kg) was similar to that during room air breathing (0.050 +/- 0.004 L/h/kg). Values for elimination half-life (7.6 +/- 0.8 versus 6.8 +/- 0.6 h) and volume of distribution at steady state (0.450 +/- 0.021 versus 0.429 +/- 0.024 L/kg) were also unchanged. The volume of distribution of theophylline was inversely related to arterial pH during oxygen therapy (pH range, 7.32 to 7.44) and during room air breathing (pH range, 7.33 to 7.47). Although hypoxemia does not alter theophylline clearance in patients with COPD, theophylline loading doses may need adjustment according to arterial pH because of an effect on volume of distribution.