Peak levels are achieved 1 hour after dosing in the fasting state and 2 hours after dosing with food. There is wide individual response. Most patients who respond to therapy with trazodone do so by the end of the second week of therapy. The drug is highly protein-bound. Studies on distribution in humans are incomplete, but in animals, the drug is distributed mainly into liver, kidneys, small intestine, lungs, adrenal glands, and pancreas, and is shown to cross the blood-brain barrier.
Trazodone is excreted into breast milk.
Metabolism in the liver is extensive. None of the metabolites is believed to be pharmacologically active. There is wide individual variation in clearance, which appears to take place in a biphasic manner. Drug accumulation in plasma can occur in some patients. Trazodone should not be used during the acute recovery period following myocardial infarction.