Phencyclidine disposition after intravenous and oral doses

Area of Science:

• Pharmacology
• Drug Metabolism
• Toxicology

Background:

• Phencyclidine (PCP) is a dissociative anesthetic with a complex pharmacokinetic profile.
• Understanding PCP's absorption, distribution, metabolism, and excretion (ADME) is crucial for clinical management and forensic toxicology.

Purpose of the Study:

• To quantify the excretion and bioavailability of Phencyclidine (PCP) in humans.
• To characterize the metabolic pathways and pharmacokinetic parameters of PCP.

Main Methods:

• Administration of radiolabeled [3H]-Phencyclidine (PCP) hydrochloride via intravenous (0.1 or 1 mg) and oral (1 mg) routes to male subjects.
• Collection and analysis of urine, feces, and perspiration for drug and metabolite recovery.
• Measurement of plasma concentrations, blood/plasma ratios, plasma binding, and saliva levels.
• Determination of pharmacokinetic parameters including half-life, volume of distribution, and clearance.

Main Results:

• Oral bioavailability of PCP was estimated at 72%.
• Approximately 72.8% of the IV dose was recovered in urine, with 16% as parent drug and 31% as hydroxylated metabolite conjugates.
• Apparent terminal phase half-life averaged 21 hours, with a volume of distribution of 6.2 L/kg.
• PCP is primarily cleared by metabolism, with renal clearance accounting for only about 9% of total clearance.

Conclusions:

• Phencyclidine (PCP) is extensively metabolized in humans.
• The pharmacokinetic profile suggests significant distribution and a relatively long elimination half-life.
• Metabolism is the principal route of PCP elimination from the body.