Pharmacogenomics in psychiatry - the challenge of cytochrome P450 enzyme phenoconversion and solutions to assist precision dosing.

Pharmacogenomic (PGx) testing of cytochrome P450 (CYP) enzymes may improve the efficacy and/or safety of some medications. This is facilitated by increased availability and affordability of genotyping, the development of clinical practice PGx guidelines and regulatory support. However, the common occurrence of CYP phenoconversion, a mismatch between genotype-predicted CYP phenotype and the actual CYP phenotype, currently limits the application of PGx testing for precision dosing in psychiatry. This review proposes a stepwise approach to assist precision dosing in psychiatry via the introduction of PGx stewardship programs and innovative PGx education strategies. A future perspective on delivering precision dosing for psychiatrists is discussed that involves innovative clinical decision support systems powered by model-informed precision dosing.

Safe disposal of prescribed medicines.

The National Return and Disposal of Unwanted Medicines Program provides a free and safe method for the disposal of unwanted and expired medicines. This stops drugs being dumped in landfill and waterways. An audit showed that over 600 tonnes of medicines are returned through the program. A substantial proportion of these medicines were still within their expiry dates. Salbutamol, insulin and frusemide are the most commonly discarded medicines. More than $2 million of public money is wasted each year. Hoarding and non-adherence to treatment contribute to waste. Health professionals may be able to help minimise waste by informing patients about the importance of completing prescribed courses of treatment, and discouraging them from hoarding medicines after reaching the safety net threshold on the Pharmaceutical Benefits Scheme. Prescribe no more than the required quantity of medicines. When starting a new therapy, prescribe a minimal quantity in case the drug is unsuitable for the patient. Advise patients to return all unwanted medicines to a pharmacy for disposal.

Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients.

BACKGROUND: Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam. METHODS/DESIGN: This is an observational pharmacokinetic study of patients with trauma (cefazolin) or with sepsis (piperacillin-tazobactam). Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration of the antibiotic. Participants will be administered sinistrin, indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes resulting from pathology. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters of antibiotics. DISCUSSION: The study will describe cefazolin and piperacillin-tazobactam concentrations in plasma and the interstitial fluid of tissues in trauma and sepsis patients respectively. The results of this study will guide clinicians to effectively dose these antibiotics in order to maximize the concentration of antibiotics in the interstitial fluid of tissues.