Abstract
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.
Similar content being viewed by others
References
Piafsky, C. M., Sitar, D. S., Rangno, R. E., Olgilvie, R. I. (1977) Clin. Pharmacol. Ther. 21, 310–316.
Adams, F. R., Vandemark, F. L., Schmidt, G. J. (1976) Clin. Chemistry 22, 1903–1906.
Rocci, M. L. Jr., Jusko, W. J. (1983), Comput. Programs Biomed. 16, 203–216.
Benet, L. Z., Galeazzi, R. L. (1979) J. Pharm. Sci. 68, 1071–1074.
Lohmann, S. M., Miech, R. P. (1976) J. Pharmacol. Exp. Ther. 196, 213–225.
Abrams, K. S., Elliott, H. W. (1974) J. Pharmacol. Exp. Ther. 189, 285–291.
Milthers, K. (1962) Acta Pharmacol. Toxicol. 19, 149–155.
George, C. F. (1979) Clin. Pharmacokin. 4, 433–448.
Brunk, S. F., Delle, M. (1974) Clin. Pharmacol. Ther. 16, 51–57.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Rocci, M.L., Mojaverian, P. & Saccar, C.L. Morphine Inhibition of Theophylline Clearance. Pharm Res 1, 231–233 (1984). https://doi.org/10.1023/A:1016329515327
Issue Date:
DOI: https://doi.org/10.1023/A:1016329515327