PHARMACOKINETICS OF ZIMELIDINE IN HUMANS - PLASMA-LEVELS AND URINARY-EXCRETION OF ZIMELIDINE AND NORZIMELIDINE AFTER INTRAVENOUS AND ORAL-ADMINISTRATION OF ZIMELIDINE

Five healthy adults were administered [the antidepressant] zimelidine [(Z)-3-(4-bromphenyl)-N,N-dimethyl-3-(3-pyridyl) allylamine] orally (150 mg) and by i.v. infusion (20 mg) in a crossover design. Blood and urine samples were collected for a period of 28 h after dosing and the concentrations of zimelidine and norzimelidine determined. There was no significant difference in terminal phase half-life [t1/2] of zimelidine after oral (4.7 h .+-. 1.3 SD) or i.v. dosing (5.1 h .+-. 0.7 SD). An average of 50% of the ingested oral dose reached the systemic circulation. Excretion of unchanged zimelidine in urine was on average 1.26% of the i.v. dose. It appears that zimelidine is completely absorbed from the gastrointestinal tract and 1st-pass metabolism in the liver reduces the bioavailability to 50%. The mean plasma t1/2 for norzimelidine was 22.8 h. The area under the plasma concentration time curve for norzimelidine after oral administration was 92% of that after i.v. administration. The plasma concentration of both zimelidine and norzimelidine are predicted to approach steady-state within 3-5 days.