By A. N. Sirjaev
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Additional info for Statistical Sequential Analysis
Cell Mol Neurobiol 19:511–532, 1999 Linnet K: Glucuronidation of olanzapine by cDNA-expressed human UDP-glucuronosyltransferases and human liver microsomes. Hum Psychopharmacol 17:233– 238, 2002 Linnet K, Olesen OV: Free and glucuronidated olanzapine serum concentrations in psychiatric patients: influence of carbamazepine comedication. Ther Drug Monit 24:512–517, 2002 Parker AC, Pritchard P, Preston T, et al: Induction of CYP1A2 activity by carbamazepine in children using the caffeine breath test.
Discussion This is an example of an inhibitor added to a substrate. Clozapine’s metabolism occurs primarily at 1A2. Enzymes 3A4 and 2C19 are also significant contributors, with 2D6 and 2C9 playing only minor metabolic roles (Eiermann et al. 1997; Olesen and Linnet 2001). Caffeine is both a substrate and a reasonably potent competitive inhibitor of 1A2 (Hartter et al. 2003; Miners and Birkett 1996). However, despite the primary role of 1A2, the auxiliary pathways for clozapine’s metabolism mitigate the ability of caffeine to significantly raise clozapine levels.
She complained to her psychiatrist at length about this weight gain, ultimately threatening to stop all of her medications unless he addressed this issue to her satisfaction. The psychiatrist rather reluctantly added topiramate (Topamax), titrating up to a dosage of 200 mg/day. Although the patient did not lose weight, she did not gain any further weight. She did not experience any difficulties with cognition or paresthesias. R. Oesterheld, personal communication, May 2002). Discussion This is an example of an inducer added to a substrate.