ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine.

Clozapine (CZ) has superior efficacy to other antipsychotic agents in the treatment of schizophrenia and has been extensively used in clinical practice. ATP-binding cassette (ABC) transporter proteins are responsible for the distribution of various molecules as well as drugs across extracellular and intracellular membranes, including the blood-brain barrier. Genetic variations in these proteins can account for differences in treatment response.

Ultrarapid clozapine metabolism and CYP2D6 gene duplication in a patient with schizophrenia.

An optimal clozapine serum level is required for both optimization of clinical response and minimization of troublesome or some of the life-threatening side effects. Serum levels can be influenced by comedication that can cause phenoconversion. When norclozapine/clozapine serum levels and ratios are consistently and significantly lower/higher than expected and there are no concomitant drugs that could account for these findings, further investigation of the genetic variants of CYP1A2, 2D6 and 3A4 are warranted.

Cases of adverse reaction to psychotropic drugs and possible association with pharmacogenetics.

Thousands of samples for pharmacogenetic tests have been analysed in our laboratory since its establishment. In this article we describe some of the most interesting cases of CYP poor metabolisers associated with adverse reactions to psychotropic drugs. Prevention of disease/illness, including Adverse Drug Reaction (ADR), is an aim of modern medicine.

Warfarin toxicity and individual variability-clinical case.

Warfarin is a widely used anticoagulant in the treatment and prevention of thrombosis, in the treatment for chronic atrial fibrillation, mechanical valves, pulmonary embolism, and dilated cardiomyopathy. It is tasteless and colorless, was used as a poison, and is still marketed as a pesticide against rats and mice. Several long-acting warfarin derivatives-superwarfarin anticoagulants-such as brodifacoum, diphenadione, chlorophacinone, bromadiolone, are used as pesticides and can produce profound and prolonged anticoagulation.

CYP2D6 genotyping by liquid chromatography-electrospray ionization mass spectrometry.

Genetic polymorphisms can significantly affect the enzyme activity of the drug metabolizing enzyme Cytochrome P450 2D6 (CYP2D6; OMIM 124030). Accordingly, CYP2D6 genotyping is considered as a valid approach to predict the individual CYP2D6 metabolizing status. We introduce ion-pair reversed-phase high-performance liquid chromatography-electrospray ionization mass spectrometry (ICEMS) as method for the characterization of single base variants, small deletions, and insertions in the CYP2D6 gene.

Pharmacogenetics and gender association with psychotic episodes on nortriptyline lower doses: patient cases.

The variation in individual responses to psychotropic drug treatment remains a critical problem in the management of psychotic disorders. Although most patients will experience remission, some patients may develop drug-induced adverse effects that may range from troublesome to life threatening. Antidepressants are freely prescribed by general practitioners, and there should be constant awareness in the medical community about possible serious side effects.

Cytochrome P450 loss-of-function polymorphism genotyping on the Agilent Bioanalyzer and clinical application.

Responses to toxins and drugs, even to standard medical drug treatment regimens, can vary significantly between individuals. Similar dosages can have divergent results due to polymorphisms in the genes that code for the enzymes responsible for the metabolism of drugs. The focus of this report is to describe our exploration of the personalized medicine approach for patient care at Sydney West Area Health Service.

High-performance liquid chromatographic determination of arecoline in human saliva.

Arecoline (methyl-1,2,5,6-tetrahydro-1-methyl nicotinate) is an alkaloid found in the areca catechu nut which is a major component of the 'betel quid' chewed by a large proporation of the population in India, South Asia and the South Pacific islands. It is commonly associated with the development of oral leukoplakia, oral submucous fibrosis and oral cancer. We have developed a new ion-pairing reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of arecoline in saliva, using arecaidine (1,2,5,6-tetrahydro-1-methylnicotinic acid) as an internal standard.