Chronopharmacology of amitriptyline.

Side effects of decreased salivation and sedation were more marked when a single dose of amitriptyline was taken orally in the morning than in the evening. These dynamic differences were due to alteration in kinetics. Absorption of the drug was more rapid in the morning, although other kinetic parameters, especially total bioavailability, were unchanged. Thus, in the case of this drug, chronopharmacologic differences were due to a change in rate of absorption. The present practice of giving a single dose of drug in the evening is justified on the basis that it induces fewer side effects without a loss in therapeutic efficacy.