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AimsTo characterize the population pharmacokinetics of indometacin in preterm infants with symptomatic patent ductus arteriosus and to investigate the influence of various factors on the response to treatment. MethodsData were collected from 35 infants (gestational age 25-34 weeks; postnatal age 1-77 days) in neonatal units in Belfast and Copenhagen. Infants received an initial course of up to three doses of intravenous indometacin (0.1-0.2 mg kg -1 ) as considered appropriate by the treating physician. For those infants who did not respond to therapy or in whom the ductus reopened, a second course was sometimes g iven. Population analysis of the 185 plasma concentrations obtained was conducted using NONMEM and pharmacokinetic and demographic differences between responders and nonresponders were compared. ResultsThe concentration-time course of indometacin was best described by a one-compar tment model. The final population parameter estimates of clearance (CL) and volume of distribution (V) (standardized to the median weight of 1.17 kg) were 0.00711 l h -1 and 0.266 l, respectively. CL increased from birth by approximately 3.38% per day and V by approximately 1.47% per day. Concomitant digoxin therapy resulted in a 30% decrease in V. Interindividual variability in CL and V was 41% and 21%, respectively. Interoccasion variability for CL was 43%. Residual variability corresponded to a standard deviation of 0.148 mg l -1 . Closure occurred in 75% of infants with a plasma concentration ≥ 0.4 mg l -1 24 h after the last dose. ConclusionsDosing regimens for indometacin should take into account the weight and postnatal age of the infant and any concomitant digoxin therapy. The population estimates can be used to determine typical values of CL and V allowing the prediction of individualized doses of indometacin that should increase the probability of achieving a 24 h plasma concentration ≥ 0.4 mg l -1 . Although the pharmacokinetic estimates will be affected by both interindividual and within-individual variation, it is anticipated that this approach will decrease the variability of exposure and optimize treatment outcome.J. M. Smyth et al. 25058 :3 Br J Clin Pharmacol

To determine the acute pharma‐cokinetics of prilocaine in intravenous regional anaesthesia (IVRA), plasma prilocaine levels before and after tourniquet release were measured for sixteen patients (including six children) with forearm fractures. A dose of 2.5mg/kg was used with a minimum cuff occlusion time of 20 minutes. No patients had detectable drug levels prior to tourniquet release. Peak drug concentrations were reached within 10 minutes of tourniquet release in all patients. Average peak drug concentration was 1.23mcg/ml. By 30 minutes, drug levels had reached an average of 0.34mcg/ml (range <0.3–0.6mcg/ml). The pharmacokinetic curves of the children were similar in profile to the adults, with analysis of variance failing to demonstrate a significant difference between curves. In no patients did prilocaine reach toxic levels. These results show that prilocaine used at a dose of 2.5 mg/kg is safe and that an observation period of 30 minutes following IVRA is adequate. IVRA does not appear to be contraindicated in children.

Residents from residential aged care services (RACS) (i.e. nursing homes) many of whom are frail or disabled, are frequently transferred to ED for treatment of acute episodes of illness or injury. This review scoped the research related to the ways in which frailty or activities of daily living (ADL) measures are used for clinical purposes, either prior to the transfer of patients to ED or in ED themselves. A search for original studies up to June 2021 that included participants aged 65 years or over was conducted across four databases. Abstracts were first reviewed, leading to full text screening and article selection. Thirty‐four studies were included in the scoping review. Most of the ADL and frailty assessments were conducted in residential aged care settings. In seven studies, ADL or frailty assessments in the aged care setting contributed to reduced transfer rates to ED. No results were found that associated the assessment of ADL or frailty with decisions related to treatment in the ED. A single ED study involved specialist emergency nursing in an ED as an intervention which included frailty assessment and led to decreased hospitalisation. This scoping review confirms an opportunity for further research into the ways frailty and ADL assessments are used for decision making in relation to the transfer of frail older people to ED, including how these assessments influence their treatment.