The antipsychotic clozapine is metabolized by the polymorphic human microsomal and recombinant cytochrome P450 2D6.

摘要: A large interindividual variability for clozapine bioavailability and plasma steady-state concentrations clearance exists. The enzymatic system which is involved in metabolism has not been fully characterized, yet structurally related tricyclic drugs have found to be metabolized by cytochrome P450 2D6 (CYP2D6), polymorphically expressed humans. involvement of CYP2D6 fluperlapine was studied with human liver microsomes recombinant RT2D6 7-8 (RT2D6) cells, specifically express CYP2D6. Clozapine its structural analog both bind the active site CYP2D6, as demonstrated competitive inhibition dextromethorphan at inhibitor up 40 microM. constants (Ki) were about 4 microM from liver. exhibited a higher constant 18.7 but difference statistically significant (P less than .05). These are close 0.3 3 achieved during therapy. Both also cells produced number metabolites clozapine, whereas only single metabolite obtained fluperlapine. identified; however, they different N-oxide N-demethyl clozapine. 7-hydroxy fluperlapine, major vivo. In conclusion, drug-drug interactions on binding polymorphic could contribute observed kinetics humans.(ABSTRACT TRUNCATED AT 250 WORDS)