Summary
The effect of different intravenous infusions on the absolute bioavailability of theophylline from a sustained-release formulation has been investigated. Oral administration of 750 mg theophylline (2 capsules Euphylong 375) was referenced to intravenous aminophylline infusions corresponding to 506 mg theophylline over 8 h (63 mg·h−1) in Study 1, and to 749 mg theophylline over 14 h in Study 2. A reduction in the infusion rate from 69 to 33 mg·h−1 was made in Study 2 after 8 h in order to mimic the concentration/time profile of the oral formulation as closely as possible. The absolute bioavailability was 100 (89, 115) % in Study 1 and 88 (73, 105) % in Study 2.
The lower clearance values and, as a consequence, the lower bioavailability ratios observed with the higher intravenous dose, although not significant, indicate that the absolute bioavailability of theophylline might appear to depend on the choice of the intravenous reference standard.
References
Anonymous (1985) Entwurf der APV-Richtlinie: Untersuchungen zur Bioverfügbarkeit, Durchführung und Beurteilung. Pharm Ind 47: 1016–1019
Dengler HJ, Beuckelmann I, Tuerk A, Vögele D (1981) Die mittlere Verweildauer — Ein Maß zur Bewertung der Bioverfügbarkeit eines retardierten Theophyllin-Präparates. In: Rietbrock N, Woodcock BG, Staib AH (eds) Theophylline and other methylxanthines. Proceedings of an International Symposium, Frankfurt/Main 29th and 30th May 1981. Vieweg, Braunschweig, FRG, pp 83–90
Flühler H, Grieve AP, Mandallaz D, Mau J, Moser HA (1983) Bayesian approach to bioequivalence assessment: An example. J Pharm Sci 72: 1178–1181
Greenblatt H, Duhme DW, Koch-Weser J, Smith TW (1974) Intravenous digoxin as bioavailability standard: Slow infusion and rapid injection. Clin Pharmacol Ther 15: 510–513
Gundert-Remy U, Hildebrandt R, Hengen N, Weber E (1983) Non-linear elimination processes of theophylline. Eur J Clin Pharmacol 24: 71–78
Jonkman JH, Tang D, Upton RA, Riegelman S (1981) Measurement of excretion characteristics of theophylline and its major metabolites. Eur J Clin Pharmacol 20: 435–441
Riegelman S, Collier P (1980) The application of statistical moment theory to the evaluation of in vivo dissolution time and absorption time. J Pharmacokinet Biopharm 8: 509–534
Schulz HU, Steinijans VW, Gabel H (1984) Differences in steady-state plasma levels between aminophylline and theophylline sustained-release micropellets after repeated circadian dosing. Int J Clin Pharmacol Ther Toxicol 22: 621–625
Steinijans VW, Diletti E (1983) Statistical analysis of bioavailability studies: Parametric and nonparametric confidence intervals. Eur J Clin Pharmacol 24: 127–136
Steinijans VW, Schulz HU, Beier W, Radtke HW (1986) Once daily theophylline: Multiple-dose comparison of an encapsulated micro-osmotic system (Euphylong) with a tablet (Uniphyllin). Int J Clin Pharmacol Ther Toxicol 24: 438–447
Tang-Liu DD, Williams RL, Riegelman S (1982) Nonlinear theophylline elimination. Clin Pharmacol Ther 31: 358–369
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Steinijans, V.W., Schulz, H.U., Böhm, A. et al. Absolute bioavailability of theophylline from a sustained-release formulation using different intravenous reference infusions. Eur J Clin Pharmacol 33, 523–526 (1987). https://doi.org/10.1007/BF00544248
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00544248