Chest, Vol 93, 379-385, Copyright © 1988 by American College of Chest Physicians

ARTICLES

Variability in theophylline volume of distribution and clearance in patients with acute respiratory failure requiring mechanical ventilation

BJ Zarowitz, S Pancorbo, J Dubey, F Wadenstorer and J Popovich Jr
Henry Ford Hospital, Department of Pharmacy Services, Detroit 48202.

This study examines the intrasubject variability in theophylline volume of distribution (V) and clearance (CL) in critically ill, mechanically ventilated adults. Fifteen patients received two intravenous doses of theophylline approximately ten hours apart. Although there was no statistical difference between the mean VI (first dose, 0.51 L/kg) and V2 (second dose, 0.47 L/kg), the absolute difference between measurements of 0.15 L/kg was statistically significant (p less than .05). Range of differences follows: between VI and V2, 3.8 to 72.4 percent (mean, 33.5 percent); between CL1 and CL2, 6.1 to 100 percent (mean, 32.2 percent). Absolute difference between clearances was 0.019 L/kg/hr. A comparative error analysis revealed an absolute difference for V of 27.9 percent and for CL of 37 percent. Considerable intra- subject variability was shown for theophylline V and CL in these critically ill adults. Variability in V was not significantly different than variability in CL, and may result in severe underdosing or overdosing.