British journal of clinical pharmacology
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Br J Clin Pharmacol · Jan 2019
Observational StudyPopulation pharmacokinetic modelling of intravenous paracetamol in fit older people displays extensive unexplained variability.
Paracetamol is the analgesic most used by older people. The physiological changes occurring with ageing influence the pharmacokinetics (PK) of paracetamol and its variability. We performed a population PK-analysis to describe the PK of intravenous (IV) paracetamol in fit older people. Simulations were performed to illustrate target attainment and variability of paracetamol exposure following current dosing regimens (1000 mg every 6 h, every 8 h) using steady-state concentration (Css-mean ) of 10 mg l-1 as target for effective analgesia. ⋯ The target concentration was achieved in the average patient with 1000 mg every 6 h, while every 8 h resulted in underdosing for the majority of the population. Furthermore, due to a large (unexplained) interindividual variability in paracetamol PK a relevant proportion of the fit older people remained either under- or over exposed.
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Br J Clin Pharmacol · Jan 2019
Comparative StudyPrevalence and incidence of prescription opioid analgesic use in Australia.
The aims of the current study were to determine the prevalence and incidence of prescription opioid analgesic use in Australia and compare the characteristics of people with and without cancer initiating prescription opioid analgesics. ⋯ Rates of opioid use have remained high since 2013, with approximately 3 million adults using opioids and over 1.9 million adults initiating opioids each year. Between 2013 and 2017, opioid prevalence has slightly increased but incidence has decreased. People without cancer account for the majority of opioid use and are more likely to be initiated on short-acting and weak opioids. Initiation of strong opioids has increased over time, reinforcing concerns about increased use and the harms associated with strong opioids in the community.
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Massive metformin overdose can cause metabolic acidosis with hyperlactatemia. A 55-year-old woman presented 5 h after multidrug overdose, including 132 g extended-release metformin. Continuous venovenous haemodiafiltration (CVVHDF) and noradrenaline were commenced due to metabolic acidosis (pH 7.0, lactate 17 mmol l-1 ) and shock. ⋯ Pharmacokinetic analysis of metformin concentrations found a reduced apparent oral clearance of 8.2 l h-1 and a half-life of approximately 30 h. During IHD, the apparent oral clearance increased to 22.2 l h-1 with an approximate half-life of 10 h. The impact of prolonged oral absorption from a pharmacobezoar and redistribution of metformin from peripheral sites (including erythrocytes) on the pharmacokinetic profile cannot be determined from the data available.
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The treatment of symptoms in people with palliative diagnoses begins with meticulous clinical assessment with treatment choice(s) selected based on an understanding of the symptom aetiology and the evidence which underpins its treatment. Increasingly, the merits of palliative care have been established earlier in the disease trajectory where treatment outcomes may include increased survival and maintenance of function. ⋯ Ideally exploration of medicinal cannabinoids should occur within a clinical trial to accelerate the evidence base to inform practice. In people with refractory symptoms, the consideration of unregistered products or off-label prescribing should be guided by the potential influences of pharmacokinetic, pharmacodynamic and drug-drug interactions, supported by an informed discussion with the patient, and regular review of net clinical benefit.