Paroxetine: pharmacokinetics, tolerance and depletion of blood 5-HT in man.

The tolerance of paroxetine (FG 7051), as well as its pharmacokinetics and reduction of 5-HT in blood, has been investigated in man. Three normal, healthy volunteers were administered the single doses 10, 25, 50, and 75 mg orally, and three volunteers received 10, 25, and 50 mg per day for seven or fourteen days. No toxic effect on blood, kidney, liver, heart or general condition was found by chemical and physical examinations. The pharmacokinetic studies revealed a dose dependent systemic availability, a rather slow elimination (t1-z2 = approximately 16 hrs), a good fit to one compartment open model, and an almost complete metabolism of the substance. 25 mg paroxetine per day gave a maximal reduction of 5-HT in the blood within 2--3 weeks (to approximately 0.03 microgram/ml). The 5-HT levels returned to the basic levels during a three to four weeks drug-free period.