METABOLISM AND DISPOSITION OF METHYLPHENIDATE-14C: STUDIES IN MAN AND ANIMALS

摘要: Threo - dl -methylphenidate- 14 C·HCl (MEPH- C·HCl) was found to be extensively metabolized in man, dog, rat and mouse. Pronounced species differences the metabolism of drug were found. In human subjects, plasma levels MEPH- C always much higher after i.v. than oral administration. After administration, 50 90% excreted urine 8 48 hours, respectively. This suggests essentially complete absorption MEPH. The main urinary metabolite deesterified product, ritalinic acid (RA), accounting for 80% dose. Upon administration dogs, 60% radioactivity 7-hour urine. major metabolites dog RA threo -2-phenyl-2-(29-piperidyl-69-one) acetic (oxo-RA). rats, both i.p. C·HCl, eliminated 30 40% feces within hours. Significant biliary excretion (25-30% 12 hours) bile-cannulated rats. besides -2-( p -hydroxyphenyl)-2-(29-piperidyl) ( -OH RA), its methyl ester MEPH)and glucuronide conjugate RA. locomotor activity MEPH, certain N-acetyl MEPH studied mice.