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PIII‐78
Author(s) -
Vermeir M.,
Boom S.,
Naessens I.,
Talluri K.,
Eerdekens M.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.286
Subject(s) - metabolite , urine , chemistry , paliperidone , excretion , feces , pharmacology , glucuronidation , glucuronide , metabolism , pharmacokinetics , endocrinology , medicine , biology , biochemistry , microsome , antipsychotic , paleontology , schizophrenia (object oriented programming) , psychiatry , enzyme
OBJECTIVES To establish the absorption, metabolism and excretion of paliperidone, a potentially new psychotropic. METHODS Male subjects (n=5) received oral 14 C‐paliperidone 1mg. Urine, feces and blood and plasma samples were collected pre‐dose and ≤1 week post‐dose, and levels of radioactive paliperidone and its metabolites were analysed. RESULTS One week post‐dose, 88.4–93.8% of the administered radioactivity was excreted: 77.1–87.1% in urine; 6.8–14.4% in feces. Unchanged drug (UD) accounted for most of the total radioactivity (TR) in plasma ≤24h post‐dose (UD vs TD=97%). Total body clearance of TR and UD averaged 97.9 and 91.0mL/min, respectively. In urine, UD accounted for 51.4–67.5% of the dose, representing 65.5–82.1% of TR excreted into urine. Besides parent drug, four metabolites were identified in urine (Table), each accounting for ≤6.5% of the dose. Two metabolites were identified in feces extracts (metabolite #16 and #9). Given the total excretion of radioactivity in feces (11.4% of the dose), fecal metabolites represented a minor fraction of the dose, each between 0.4–0.9%. No UD was found in fecal extracts.Code Biotransformation route Metabolite Mean ± SD (Expressed as % of dose)#1 Oxidative N ‐dealkylation Acid metabolite R093725 4.6 ± 1.4 #16 Benzisoxazole scission & glucuronidation R084852‐glucuronide 4.1 ± 1.0 #9 Alicyclic mono‐hydroxylation Monohydroxy‐paliperidone 3.8 ± 1.4 UD Unchanged drug Paliperidone 59.4 ± 7.1 #12 Alcohol dehydrogenation Ketone metabolite R125239 2.7 ± 1.7CONCLUSIONS Paliperidone was metabolized to a limited extent. No important metabolic interactions are expected for paliperidone. Clinical Pharmacology & Therapeutics (2005) 79 , P80–P80; doi: 10.1016/j.clpt.2005.12.286