ABSTRACT
OBJECTIVE: Limited data suggest that CYP1A2 and CYP2D6 are involved in the metabolism of olanzapine. The purpose of this study was to further elucidate the role of these enzymes in the disposition of olanzapine in vivo. METHODS: Seventeen healthy non-smoking male volunteers were included in the study. Five subjects were CYP2D6 poor metabolisers (PMs), and 12 were CYP2D6 extensive metabolisers (EMs). All subjects received a single oral dose of 7.5 mg olanzapine, and serum concentrations were measured for 96 h using gas chromatography. A cross-over study was undertaken in the 12 CYP2D6 EMs who at least 2 weeks before or after the olanzapine dose received a single oral dose of 200 mg caffeine. The concentrations of caffeine and paraxanthine were measured in saliva 10 h after caffeine intake, and the paraxanthine/caffeine ratio was calculated as a measure of CYPIA2 activity. RESULTS: A threefold inter-individual variability in oral clearance (CLoral) and maximum serum concentration (Cmax) of olanzapine was observed and a 2.3-fold inter-individual variability in CYPIA2 activity. There was no significant correlation between CYP1A2 activity and oral clearance of olanzapine (r=-0.19, P=0.56). Moreover, there were no significant differences in any of the olanzapine pharmacokinetic parameters between the CYP2D6 PMs and EMs (CLoral=0.246 l h(-1) kg(-1) and 0.203 l h(-1) kg(-1), respectively, P=0.30). CONCLUSION: Neither CYP1A2 nor CYP2D6 seem to have a dominating role in olanzapine biotransformation after intake of a single dose.
Subject(s)
Antipsychotic Agents/pharmacokinetics , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP2D6/metabolism , Pirenzepine/analogs & derivatives , Pirenzepine/pharmacokinetics , Adult , Antipsychotic Agents/administration & dosage , Area Under Curve , Benzodiazepines , Biotransformation , Cytochrome P-450 CYP1A2/genetics , Cytochrome P-450 CYP2D6/genetics , Humans , Isoenzymes , Male , Metabolic Clearance Rate , Olanzapine , Phenotype , Pirenzepine/administration & dosage , Pirenzepine/bloodABSTRACT
Frequent occurrences of pollution in natural drainage by industrial chemicals, especially pesticides, have triggered interest in the development of fast and unambiguous analytical techniques to verify these pollutants in order to facilitate rapid remedial actions. In this work, we report the development of a solid-phase microextraction (SPME) method to analyse two common industrial pesticides in water, i.e. malathion and parathion. SPME analysis facilitates direct analysis of chemical species in aqueous systems and avoids lengthy sample preparation procedures. In this study, we compare five commercially available fibres: 7 microns polydimethylsiloxane, 30 microns polydimethylsiloxane. 85 microns polyacrylate, 65 microns Carbowax-divinylbenzene and 65 microns polydimethylsiloxane-divinylbenzene fibres. Profiles of uptake by the fibres against adsorption times were established. The results obtained indicated that the polarity of the fibres is not the main factor affecting the uptake. The structures of the fibres also affected the permeation of the analytes onto the fibres. The limits of detection were determined to be in the low ppb level with a flame ionization detector. These methods have great potential for use in rapid on-site analytical work which is highly demanded in environmental studies.
