British journal of clinical pharmacology
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Br J Clin Pharmacol · Jan 2019
Multicenter StudyPopulation pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Carboplatin dosage is calculated by using the estimated glomerular filtration rate (GFR) to achieve a target plasma area under the plasma concentration-time curve (AUC). The aims of the present study were to investigate factors that influence the pharmacokinetics of carboplatin in children with high-risk neuroblastoma, and whether target exposures for carboplatin were achieved using current treatment protocols. ⋯ GFR did not appear to influence the pharmacokinetics of carboplatin after adjusting pharmacokinetic parameters for weight. This model-based approach validates the use of weight-based dosing as an appropriate alternative for carboplatin in children with either mild renal impairment or normal renal function.
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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.