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1 The pharmacokinetics of morphine, morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G) were studied in 19 ventilated newborn infants ( 24-41 weeks gestation) who were given a loading dose of 50 mg kg−1 or 200 mg kg−1 of diamorphine followed by an intravenous infusion of 15 mg kg−1 h−1 of diamorphine. Plasma concentrations of morphine, M3G and M6G were measured during the accrual to steady-state and at steady state of the diamorphine infusion. 2 Following both the 50 mg kg−1 or 200 mg kg−1 loading doses the mean steadystate plasma concentration (±s.d.) of morphine, M3G and M6G were 86±52 ng ml−1, 703±400 ng ml−1 and 48±28 ng ml−1 respectively and morphine clearance was found to be 4.6±3.2 ml min−1 kg−1. 3 M3G formation clearance was estimated to be 2.5±1.8 ml min−1 kg−1, and the formation clearance of M6G was estimated to be 0.46±0.32 ml min−1 kg−1. 4 M3G metabolite clearance was 0.46±0.60 ml min−1 kg−1, the elimination half-life was 11.1±11.3 h and the volume of distribution was 0.55±1.13 l kg−1. M6G metabolite clearance was 0.71±0.36 ml min−1 kg−1, the elimination half-life was 18.2±13.6 h and the volume of distribution was 1.03±0.88 l kg−1. 5 No significant effect of the loading dose (50 mg kg−1 or 200 mg kg−1) on the plasma morphine or metabolite concentrations or their derived pharmacokinetic parameters was found. 6 We were unable to identify correlations between gestational age of the infants and any of the determined pharmacokinetic parameters. 7 M3G5morphine and M6G5morphine steady-state plasma concentration ratios were 11.0±10.8 and 0.8±0.8, respectively. 8 The metabolism of morphine in neonates, in terms of the respective contributions of each glucuronide pathway, was similar to that in adults.

Aims-To compare the safety and efficacy of two loading doses of diamorphine in 27 ventilated newborn infants in a randomised double blind trial. Methods-Fifty or 200 mcg/lkg were infused intravenously over 30 minutes, followed by a 15 mcg/kgthour continuous infusion. Serial measurements were made of physiology, behaviour, and stress hormones. Results-Both loading doses produced small but significant falls in blood pressure. The 200 mcg/kg dose produced greater respiratory depression, and two infants deteriorated clinically, requiring resuscitation. Loading reduced respiratory effort in most of the infants, but had little effect on behavioural activity. Stress hormone concentrations were reduced at six hours in both dosage groups; differences between loading doses were not significant. Morphine, morphine-3-glucuronide, and morphine-6-glucuronide were detected in the plasma of all patients. No significant differences in concentrations between loading doses were found. Conclusions-Diamorphine reduces the stress response in ventilated newborn infants. A high loading dose confers no benefit, and may produce undesirable physiological effects. A 50 mcglkg loading dose seems to be safe and effective. (Arch Dis Child 1995; 73: F22-F26)

Objective The primary aim was to determine endocannabinoid (EC) concentrations of 2-arachidonoylglycerol (2-AG), oleoylethanolamine (OEA), palmitoylethanolamine (PEA) and anandamide (AEA) in the aqueous humour of patients, and to investigate any differences in gender and diabetic or ocular disease status.Methods and Analysis Adult participants (age >18 years) listed for a routine cataract surgery were recruited. For patients with diabetes, results from their most recent retinopathy grading were recorded. A sample of aqueous humour was removed from the anterior chamber of the patients and snap-frozen in liquid nitrogen. Levels of 2-AG, PEA, OEA and AEA were measured by liquid chromatography-tandem mass spectrometry.

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