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Nilofar Daneshi,1,2 Elizabeth Holliday,3,4 Stephen Hancock,3,4 Jennifer J Schneider,1,2 Rodney J Scott,1,2,5 John Attia,3,4 Elizabeth A Milward1,2 1Faculty of Health and Medicine, School of Biomedical Sciences and Pharmacy, 2Faculty of Health and Medicine, Centre for Bioinformatics, Biomarker Discovery and Information-Based Medicine, The University of Newcastle, Callaghan, 3Clinical Research Design, IT and Statistical Support Unit, Hunter Medical Research Institute, 4Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, Faculty of Health, University of Newcastle, 5Hunter Area Pathology Service, John Hunter Hospital, Newcastle, NSW, Australia Abstract: This study analyzed clinically actionable pharmacogenotypes for clopidogrel, warfarin, statins, thiopurines, and tacrolimus using microarray data for 2121 participants (55–85 years) from the Australian Hunter Community Study (HCS). At least 74% of participants (95% confidence interval [CI]: 72%–76%) had strong level evidence for at least one medium- or high-risk actionable genotype that would trigger a change in standard therapy under current international recommendations. About 14% of these participants (95% CI: 12%–16%) were taking medication potentially affected by the genotype in question. Furthermore, ~2.6% of all participants with medication data (95% CI: 1.4%–3.8%) had a high-risk clinically actionable genotype for a medication to which they were exposed. This represents a considerable number of people at the population level. Although relationships between genotype and health outcomes remain contentious, pharmacogenotyping of multiple variants simultaneously may have considerable potential to improve medication safety and efficacy for older people in the community. Keywords: actionable genotype, community, older adults, pharmacogenomics, pre-emptive genotyping, single-nucleotide polymorphism

Plasma morphine concentrations were measured in five cancer patients receiving long-term epidural morphine administration. Peak concentrations were observed within 1 h of dosage and concentrations then declined biexponentially. Plasma morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations were measured in two patients and plasma M3G concentrations were observed to be much higher than plasma M6G and morphine concentrations. Peak plasma M6G concentrations occurred within 1.0 h of dosing and plasma M6G concentrations then remained higher than plasma morphine concentrations. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of theophylline (i.v. aminophylline 250 mg) were studied in a balanced, double-blind crossover following the administration of oral temelastine (100 mg) or placebo, twice daily for 7 days, to 10 normal volunteers. Comparison of volumes of distribution, elimination rate constants, elimination half-lives and areas under the plasma concentration-time curve indicated that temelastine had no significant effect on theophylline pharmacokinetics. [ABSTRACT FROM AUTHOR]