Summary
We have studied the interaction of erythromycin with theophylline.
We gave ten healthy volunteers theophylline as an intravenous loading dose (5 mg·kg−1) over 1 h, followed by a maintenance infusion (0.5 mg·kg−1·h−1) for 5 h. A second infusion of theophylline was given after 9 days of treatment with 1 g erythromycin base daily, and the concentrations of theophylline were determined during the infusion periods. The concentrations of erythromycin were measured for 8 h, after one week of treatment, and also after the last erythromycin dose, simultaneously with the second theophylline infusion.
Concentrations within the therapeutic range were obtained with both drugs. A significant increase in both AUC and mean plasma concentrations of theophylline was seen during erythromycin treatment. The plasma clearance of theophylline was reduced in 9 of the 10 subjects. Renal clearance increased correspondingly, but the change was not statistically significant.
Serum concentrations of erythromycin fell significantly, by more than 30%, with concurrent theophylline medication.
We conclude that an interaction between theophylline and erythromycin, affecting both drugs, can be shown with concentrations of the drugs within the therapeutic range.
Similar content being viewed by others
References
Cummins LH, Kozak PP, Gillman SA (1976) Theophylline determinations. Ann Allergy 37: 450–451
Cummins LH, Kozak PP, Gillman SA (1977) Erythromycin's effect on theophylline blood level. Pediatrics 59: 144–145
Kozak PP, Cummins LH, Gillman SA (1977) Administration of erythromycin to patients on theophylline. J Allergy Clin Immunol 60: 149–151
Pfeifer HJ, Greenblatt DJ, Friedman P (1979) Effects of three antibiotics on theophylline kinetics. Clin Pharmacol Ther 26: 36–40
Melethil S, Dutta A, Ryan PB, Pingleton SK, Kelly SJ (1982) Steady-state urinary excretion of theophylline and its metabolites in the presence of erythromycin. Res Commun Chem Pathol Pharmacol 35: 341–344
Maddux MS, Leeds NH, Organek HW, Hasegawa GR, Bauman JL (1982) The effect of erythromycin on theophylline pharmacokinetics at steady-state. Chest 81: 563–565
Kelly SJ, Pingleton SK, Ryan PB, Melethil S (1981) No effect of erythromycin on plasma theophylline levels. Clin Res 29: 796
Jonkman JHG, Upton RA (1984) Pharmacokinetic drug interactions with theophylline. Clin Pharmacokinet 9: 309–334
Ludden TM (1985) Pharmacokinetic interactions of the macrolide antibiotics. Clin Pharmacokinet 10: 63–79
Descotes J, André, Evreux JC (1985) Pharmacokinetic drug interactions with macrolide antibiotics. J Antimicrob Chemother 15: 659–664
Hildebrandt R, Gundert-Remy Y, Möller H, Weber E (1984) Lack of clinically important interaction between erythromycin and theophylline. Eur J Clin Pharmacol 26: 485–489
Iliopoulou A, Aldhous ME, Johnston A, Turner P (1982) Pharmacokinetic interaction between theophylline and erythromycin. Br J Clin Pharmacol 14: 495–499
Edholm L-E, Ögren L (1985) Liquid chromatography in pharmaceutical development. In: Wainer IW (ed) An introduction. Aster Publishing Corp, Springfield, Oregon, pp 345–373
Vercelloni M, Cogo R, Albertini A, Granata M, Rosaschino F (1986) Aminophylline blood levels with concomitant erythromycin therapy in relapsed chronic obstructive lung disease. J Int Med Res 14: 131–136
Lesko LJ (1979) Dose-dependent elimination kinetics of theophylline. Clin Pharmacokinet 4: 449–459
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Paulsen, O., Höglund, P., Nilsson, L.G. et al. The interaction of erythromycin with theophylline. Eur J Clin Pharmacol 32, 493–498 (1987). https://doi.org/10.1007/BF00637676
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00637676