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Disposition of phencyclidine after intramuscular administration
Archives of Toxicology. Supplement. = Archiv Fur Toxikologie. Supplement
|January 1, 1983
Summary
Radioactive phencyclidine (PCP) distributes unevenly in rat tissues, concentrating in the pancreas, salivary glands, and fat. Muscles and bones may act as significant reservoirs despite lower initial uptake.
Area of Science:
- Pharmacology
- Toxicology
- Biochemistry
Background:
- Phencyclidine (PCP) is a dissociative anesthetic with known psychoactive and toxicological effects.
- Understanding the tissue distribution and disposition of PCP is crucial for assessing its pharmacokinetic profile and potential for accumulation.
- Previous studies have indicated varied tissue distribution patterns for drugs, necessitating specific investigations for PCP.
Purpose of the Study:
- To investigate the tissue disposition of radioactive phencyclidine (PCP) in rats following single and repeated intramuscular injections.
- To determine the time course of PCP radioactivity in various tissues and identify potential accumulation sites.
- To assess the depletion rates of PCP radioactivity from different tissues after cessation of administration.
Main Methods:
- Rats were administered single or repeated intramuscular injections of 3H-phencyclidine (3H-PCP) over 23 days.
- Tissue samples from various organs (pancreas, salivary glands, mesenteric fat, brain, muscles, tendons, bones) were collected at different time points.
- Radioactivity levels in tissue homogenates were quantified using liquid scintillation counting.
- Depletion rates were analyzed by measuring radioactivity remaining in tissues 48 hours after the final injection.
Main Results:
- Peak radioactivity levels were observed 45-90 minutes after a single 3H-PCP administration.
- The pancreas, salivary glands, and mesenteric fat exhibited 4-6 fold higher radioactivity compared to brain, muscles, tendons, and bones.
- Repeated injections led to higher overall radioactivity levels, maintaining a similar distribution pattern.
- The highest percentage of depletion within 48 hours post-injection was found in the pancreas, salivary glands, and mesenteric fat.
Conclusions:
- Phencyclidine (PCP) exhibits a distinct tissue distribution pattern in rats, with preferential accumulation in the pancreas, salivary glands, and mesenteric fat.
- Despite lower initial uptake per unit mass, the large relative mass of muscles, tendons, and bones suggests they could serve as significant reservoirs for PCP or its metabolites.
- These findings contribute to a better understanding of PCP pharmacokinetics and its potential long-term disposition in the body.