Paroxetine: Pharmacokinetics, Tolerance and Depletion of Blood 5‐HT in Man

Abstract

Absiruct: 'The tolerance of paroxetinc (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 orfourteen 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 (tl,2=approximately 16 hrs), a good fit to a one compartment open model,and analmost 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 pg/nil). The 5-HT levels returned to the basic levels during a three to four weeks drug-free period.

Paroxetine: Pharmacokinetics and Cardiovascular Effects after Oral and Intravenous Single Doses in Man

“…The values for lag time, k, and elimination halflife were in good agreement with the values found in the previous study (Lund et a/. 1979b).…”

“…A basic presumption for several of the equations used is dose independent kinetics, but the present estimates of systemic availability tend to confirm the previously suggested dose dependent kinetics for paroxetine after oral administration (Lund et a/. 1979b).…”

“…In a previous study (Lund et al 1979b) a onecompartment model gave a good description of the plasma concentration data after oral administration of paroxetine. In the present study the oral data from only one subject, D , were better described by a two-compartment model.…”

“…Paroxetine in plasma was determined by a specific gas chromatographic procedure as previously described (Petersen et al 1978). Serotonin was determined fluorometrically after treatment with ophthalaldehyde as described earlier (Lund et al 1979b).…”

“…Pharmacokinetic studies in healthy volunteers given single oral doses have shown a disposition compatible with a one-compartment open model. The elimination half-life was about 16 hrs (Lund et al 1979b). Paroxetine was found to be almost completely metabolized in man, and these studies indicated a significant first pass effect as well as dose dependent kinetics.…”