Chronobiology and Asthma. II. Body-Tune-Dependent Differences in the Kinetics and Effects of Bronchodilator Medications

Abstract

Several bronchodilator medications exhibit body-time (i.e., biological rhythm)-dependent changes in their phar-macokinetics and effects. Epinephrine (Adrenalin), metaproterenol (orciprenaline), aminophylline, and ipratropium bromide all have a better effect on the tone of the airways during the night and/or morning, when bronchial patency is low, than during the day, when it is high. The pharmacokinetics of sustained-release theophyllines (SRTs) exhibit administration-time differences. Day-night dosing-time differences in the kinetics of theophylline are especially prominent in children. Generally, in day-active asthmatic children the absorption of SRTs is more rapid after a morning than an evening closing. The administration-time effect on the kinetics of SRTs also is apparent in adult patients, but the magnitude of difference between the day versus evening administrations apparently is more moderate. Initial findings from studies of unequal (morning versus evening) BID dosing schedules—more theophylline or terbutaline before bedtime than arising—reveal a better therapeutic advantage relative to equal BID dosing schedules for those patients with predominantly nocturnal symptoms.

Once-daily (OD) SRTs intended for delivery of the entire daily dose at a single time also differ quantitatively in their chronokinetics. Since asthma is mainly a nocturnal disease in many patients, it has been recommended by many that ODSRTs be taken in the evening. If taken in the morning, as is the current practice in the United States, they may not ensure therapeutic theophylline blood levels during the night when most needed. Moreover, not all ODSRTs appear suitable for once-nightly administration because of unacceptable kinetics.