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Abstract: Background and Aims: Take‐home naloxone can prevent death from heroin/opioid overdose, but pre‐provision is difficult because naloxone is usually given by injection. Non‐injectable alternatives, including naloxone nasal sprays, are currently being developed. To be effective, the intranasal (i.n.) spray dose must be adequate but not excessive, and early absorption must be comparable to intramuscular (i.m.) injection. We report on the pharmacokinetics (PK) of a specially produced concentrated novel nasal spray. The specific aims were to: (1) estimate PK profiles of i.n. naloxone, (2) compare early systemic exposure with i.n. versus i.m. naloxone and (3) estimate i.n. bioavailability. Design: Open‐label, randomized, five‐way cross‐over PK study. Setting: Clinical trials facility (Croydon, UK). Participants: Thirty‐eight healthy volunteers (age 20–54 years; 11 female). Intervention and comparator: Three doses of i.n. (1 mg/0.1 ml, 2 mg/0.1 ml, 4 mg/0.2 ml) versus 0.4 mg i.m. (reference) and 0.4 mg intravenous (i.v.) naloxone. Measurements: Regular blood samples were taken, with high‐frequency sampling during the first 15 minutes to capture early systemic exposure. PK parameters were determined from plasma naloxone concentrations. Exploratory analyses involved simulation of repeat administration. Findings: Mean peak concentration (Cmax) values for 1 mg (1.51 ng/ml), 2 mg (2.87 ng/ml) and 4 mg (6.02 ng/ml) i.n. exceeded 0.4 mg i.m. (1.27 ng/ml) naloxone. All three i.n. doses rapidly achieved plasma levels > 50% of peak concentrations (T50%) by 10 minutes, peaking at 15–30 minutes (Tmax). For comparison, the i.m. reference reached Tmax at 10 minutes. Mean bioavailability was 47–51% for i.n. relative to i.m. naloxone. Simulation of repeat dosing (2 × 2 mg i.n. versus 5 × 0.4 mg i.m. doses) at 3‐minute intervals showed that comparable plasma naloxone concentrations would be anticipated. Conclusions: Concentrated 2 mg intranasal naloxone is well‐absorbed and provides early exposure comparable to 0.4 mg intramuscular naloxone, following the 0.4 mg intramuscular curve closely in the first 10 minutes post‐dosing and maintaining blood levels above twice the intramuscular reference for the next 2 hours. [ABSTRACT FROM AUTHOR]

Aims To describe work undertaken over a 20-year period, investigating overdose characteristics among survivors, effects of acute heroin administration, clustering of risk of overdose fatality and potential interventions to reduce this fatal outcome. Methods Privileged-access interviewers obtained data from non-treatment as well as treatment samples; experimental study of drop in oxygen saturation following heroin/opiate injection; investigation of clusterings of death following prison release and treatment termination; and study of target populations as intervention work-force, including family as well as peers, and action research built into pilot implementation. Results Overdose has been experienced by about half of heroin/opiate misusers, with even higher proportions having witnessed an overdose, and with high levels of willingness to intervene. Heroin/opiates are associated with the majority of drug-related deaths, despite relative scarcity of use. Heroin injection causes a rapid drop in oxygen saturation, recovering only slowly over the next half hour. Deaths from drug overdose are greatly more likely on prison release and post-discharge from detoxification and other in-patient or residential settings. High levels of declared willingness to intervene are matched by active interventions. Both drug-using peers and family members show ability to improve knowledge and gain confidence from training. Audit study of take-home schemes finds approximately 10% of dispensed naloxone is used in real-life emergency situations. Conclusions Overdose is experienced by most users, with heroin/opiates contributing disproportionately to drug overdose deaths. High-risk times (e.g. after prison release) are now clearly identified. Peers and family are a willing potential intervention work-force, but are rarely trained or given pre-supply of naloxone. Large-scale naloxone provision (e.g. national across Scotland and Wales) is now being delivered, while large-scale randomized trials (e.g. N-ALIVE prison-release trial) are finally under way. Better naloxone products and better-organized provision are needed. The area does not need more debate; it now needs proper implementation alongside good scientific study. [ABSTRACT FROM AUTHOR]

Objective Intramuscular (i.m.) pethidine is used worldwide for labour analgesia and i.m. diamorphine usage has increased in the UK in the last 15 years. This trial aims to ascertain the relative efficacy and adverse effects of diamorphine and pethidine for labour pain. Design Prospective, parallel-arm randomised controlled trial with blinding of participants, care-givers and outcome assessors. Setting Maternity units in two District General Hospitals in the UK. Population After written informed consent, 484 women were randomised and recruited (244 diamorphine, 240 pethidine). Inclusion criteria included women 16 years or older, established labour, singleton pregnancy, 37-42 weeks of gestation and weight 60-120 kg. Methods On request of i.m. analgesia, participants received either 150 mg pethidine or 7.5 mg diamorphine based on computer-generated block randomisation. Main outcome measures Maternal-reduction in pain intensity from baseline (10-cm visual analogue scale) at 60 minutes and over the 3-hour period after drug administration. Neonatal-requirement for resuscitation and Apgar score at 1 minute. Results Diamorphine provided modestly improved pain relief at 60 minutes, mean difference 1 cm (95% confidence interval [ CI] 0.5-1.5), and over the 3 hours, mean difference 0.7 cm (95% CI 0.3-1.1). However, average length of labour in women receiving diamorphine was 82 minutes longer (95% CI 39-124) and therefore they experienced more pain overall. There were no statistically significant differences in primary neonatal outcomes. Conclusions There is a modest difference between the analgesia provided by diamorphine or pethidine for labour analgesia but diamorphine is associated with significantly longer labours. [ABSTRACT FROM AUTHOR]

Data were collected on 1,074 opiate detoxifications conducted with lofexidine, from 40 drug dependency units in the United Kingdom. 671 patients (62.5%) attempted a detoxification in the community, with the remainder attempting an inpatient detoxification. Patients completing the detoxification started on a mean dose of 0.8 mg/day (median 0.6 mg/day), titrating to a mean dose of 2.2 mg/day (median 1.6 mg/day) and detoxifying in a mean of 10 days (median 10 days). Overall 614 patients (60.4%) successfully completed the detoxification. The most frequently recorded adverse events were dry mouth (5.3%), dizziness (8.5%) and sedation (6.6%). In conclusion, lofexidine is widely and successfully used to rapidly detoxify patients from a range of opiates. [ABSTRACT FROM AUTHOR]

The author presents a discussion of "Does paying service providers by results improve recovery outcomes for drug misusers in treatment in England?" by A. Jones et al. He mentions the shift to local government funding, the difficulties of treating opioid abuse, and the use of various forms of behavior modification to support treatment.