Table 1.

Selected drugs with circadian variation in pharmacokinetics and pharmacodynamics

Drug	Variation
Propranolol	Absorbed more rapidly after morning dosage than after night dosage.w1 However, chronokinetics cannot explain circadian changes in effects. Circadian variation in sympathetic tone and vascular reactivity is mainly responsible for circadian changes in effects of propranololw2
Nifedipine	Pharmacokinetics of immediate release but not sustained release preparation depends on time of day. Immediate release nifedipine had higher Cmax (peak concentration) and shorter tmax (time to peak concentration) after morning dosing than after evening dosing, and bioavailability in the evening was reduced by about 40%w3
Digoxin	Time to reach maximum plasma concentration was significantly shorter after 8 am dosing (54 min) than after 8 pm dosing (96 min)w4
Diltiazem	Diltiazem HCI extended release tablets administered in the evening (10 pm) had 17% and 22% greater bioavailability than morning administration (7 am or 8 am) under single dose and steady state conditions, respectivelyw5
Enalapril	Subchronic treatment at 7 am significantly reduced blood pressure during the day but was less effective at night. Subchronic dosing at 7 pm significantly decreased night time blood pressure followed by a slow increase during the day, with no effect on elevated afternoon valuesw6
Theophylline	Intake of a timed release formulation of theophylline at 3 pm achieved therapeutic drug concentrations during the night and avoided toxic concentrations during the day.w7 A new asymmetric dosage regimen of sustained release formulation of theophylline glycerinate (one tablet in the morning and four tablets in the evening) produced a steady and effective concentration of theophylline in plasma for the whole day, especially in the eveningw8
Inhaled steroids	Optimal once daily dosing of inhaled steroid is between 3 pm and 5 30 pmw9
Prednisone	Oral prednisone has been shown to be much more effective in improving several features of nocturnal asthma when administered at 3 pm rather than at 8 amw10
Cimetidine	Administration of H2 antagonists at bedtime is more effective than administration in the morning. Nocturnal administration not only reduces acid secretion more effectively but also promotes ulcer healing and reduces ulcer recurrencew11
Ibuprofen	After administration of ibuprofen press coated formulation, both the rate and extent of absorption were lower when dosing took place at 8 am than when dosing took place at 10 pm. The difference between morning and evening dosing of the immediate release formulation was minimalw12