Chemical and biopharmaceutical aspects of theophylline and its derivatives

Summary

Although the N-substituted derivatives of theophylline are commonly described as ‘theophylline derivatives with uses similar to those of aminophylline’ and approximate equivalents in theophylline content are given, they have different pharmacological and pharmacokinetic properties which must be taken into account. Data on the chemical, biopharmaceutic and pharmacokinetic properties of theophylline, its salts and some N-substituted derivatives are discussed. After oral administration, theophylline and its salts, aminophylline and choline theophyllinate, arequickly andcompletely absorbedand optimal blood concentrations of theophylline (10 to 20 μg/ml) are readily attained, depending on the release characteristics of the formulation. In contrast, however, the N-substituted derivatives such as acephylline, etophylline and diprophylline, although more soluble than theophylline, are incompletely absorbed and whilst proxyphylline is completely absorbed, none of these derivatives dissociate to theophylline in vitro or in vivo. Moreover, their elimination kinetics and the relatively high blood concentrations considered necessary, from the limited data available, to result in a therapeutic level mean that unrealistically high doses of these compounds would be necessary compared with those of theophylline in the long-term therapy of chronic asthmatics.

Key Words::

• Theophylline
• xanthine alkaloids
• biopharmaceutics