Morphine inhibition of theophylline clearance.

The effects of morphine on the single dose pharmacokinetics of theophylline were examined in two groups (6 rats/group) of male Sprague-Dawley rats after the administration of theophylline (6.25 mg/kg) alone and in conjunction with a 5 mg /kg I.V. dose of morphine sulfate. Concomitant morphine administration resulted in a 55 % reduction in theophylline clearance (0.14 ± 0.04 vs. 0.31 ± 0.061 · h(-1) kg(-1); p. < 0.0005). The reduction in theophylline clearance with morphine administration was accompanied by a significant prolongation in theophylline half-life (3.5 ± 1.5 vs. 1.4 ± 0.35 h; p < 0.02). No changes in the volume of distribution of theophylline occurred with co-administration of morphine. The mechanism of this pharmacokinetic interaction may be partially related to competition between theophylline and morphine for enzymes which metabolize these compounds.