Current study results from the report, 'In vitro and in vivo evaluation of the inhibition potential of risperidone toward clozapine biotransformation,' have been published. In this recent report published in the British Journal of Clinical Pharmacology, researchers in Sydney, Australia conducted a study "To study the impact of risperidone (RISP) on clozapine (CLZ) biotransformation in vitro in microsomal fractions containing varying expression of CYP oxidases and in vivo in patients. Human liver microsomes (n=11) were assessed for expression of CYPs 1A2, 2D6 and 3A4, because these enzymes mediate RISP and CLZ oxidation."

"Inhibition of CLZ oxidation by RISP was assessed. Plasma CLZ elimination was estimated in patients with schizophrenia who received either CLZ alone or the CLZ-RISP combination (n=10 per group). (i) The CYP3A4 and CYP1A2 inhibitors ketoconazole and fluvoxamine inhibited CLZ oxidation to varying extents in individual microsomal fractions. (ii) RISP did not inhibit CLZ oxidation, regardless of variations in CYP expression. (iii) RISP co-administration did not impair CLZ clearance. No evidence was found for CYP-mediated inhibitory or pharmacokinetic interactions between RISP and CLZ," wrote M. Chetty and colleagues, University of Sydney, Faculty of Pharmacy (see also Pharmaceuticals).

The researchers concluded: "Occasional literature reports of such interactions may involve other pathways that participate in CLZ disposition."

Chetty and colleagues published their study in British Journal of Clinical Pharmacology (In vitro and in vivo evaluation of the inhibition potential of risperidone toward clozapine biotransformation. British Journal of Clinical Pharmacology, 2009;68(4):574-9).

For additional information, contact M. Chetty, University of Sydney, Faculty of Pharmacy, Sydney, NSW 2006, Australia.

The publisher's contact information for the British Journal of Clinical Pharmacology is: Blackwell Publishing Inc., 350 Main St., Malden, MA 02148, USA.