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 zimelidine orally (150 mg) and by intravenous infusion (20 mg) in a crossover design. Blood and urine samples were collected for a period of 28 hours after dosing and the concentrations of zimelidine and norzimelidine determined. There was no significant difference in terminal phase half-life of zimelidine after oral (4.7 h +/- 1.3 SD) or intravenous 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 intravenous dose. It appears that zimelidine is completely absorbed from the gastrointestinal tract and "first-pass metabolism" in the liver reduces the bioavailability to 50%. The mean plasma half-life for norzimelidine was 22.8 h. The area under the plasma concentration time curve for norzimelidine after oral administration was 92% of that after intravenous administration. The plasma concentration of both zimelidine and norzimelidine are predicted to approach steady-state within 3--5 days.
D000284:Administration, Oral; D000328:Adult; D000928:Antidepressive Agents / Q000378:metabolism*; D001977:Brompheniramine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D011725:Pyridines / Q000378:metabolism*; D015031:Zimeldine / Q000031:analogs & derivatives
D000928:Antidepressive Agents; D011725:Pyridines; D015031:Zimeldine; C017578:norzimelidine; D001977:Brompheniramine