Background:Droperidol is used parenterally to treat nausea and vomiting, migraine and acute behavioural disturbance. Intranasal use is not reported for droperidol. Intranasal drug administration reduces need for intravenous line placement and risk of needle-stick.Objective:To model population pharmacokinetics of intranasal droperidol.Method:Single doses of intranasal and intravenous droperidol (0.02 mg/kg) were studied in an open-label crossover-trial in seven volunteers with a 1-week washout period. Blood samples collected over 10-h were analysed by liquid chromatography tandem mass spectrometer. Droperidol plasma concentrations following intravenous and intranasal administration were subjected to non-compartmental analysis and population pharmacokinetic modelling using S-ADAPT. Monte Carlo simulations were conducted for various potential intranasal dosage regimens.Results:The droperidol concentration-time profiles following intravenous and intranasal administration were best described by a model with two equilibrating disposition compartments and linear elimination. The apparent elimination clearance for intranasal dosing was 87.9 L/h and apparent central volume of distribution 18.2 L. Monte Carlo simulations of 5 mg droperidol (corresponding to the maximum volume that can be practically administered intranasal at a time) given intranasally at 0 and 5 min or 0 and 10 min indicated peak concentrations would reach those seen at 25 min after single intravenous administration of 1.5 mg. No adverse clinical effects or QT interval prolongation were observed.Conclusion:Given the reduced bioavailability of intranasal droperidol, Monte Carlo simulations suggested that it could potentially be used at a higher dose (2.5–5 mg) than currently used intravenously in clinical trials assessing the effectiveness in treatment of nausea, vomiting and migraine.

The authors report a case of atherosclerotic stroke in a 46-year-old recreational bodybuilder with a 20 year history of anabolic-adrenergic steroid (AAS) abuse. Cerebrovascular accident (CVA) occurred during his third week of hospital admission for an acute abdomen and on day 8, postemergency laparotomy. CVA presented with collapse, generalised seizures, reduced Glasgow Coma Score and severe hypertension. He was subsequently admitted to the intensive care unit (ICU), where initial investigations did not illustrate an underlying diagnosis. By day 4 in ICU, there had been no significant clinical improvement and radiological investigations were repeated, identifying a left frontal lobe infarct in the middle cerebral artery territory. The authors propose CVA was secondary to AAS. After a prolonged and complicated period of rehabilitation, he has been discharged home; he requires carers due to dyspraxia and is mobilising independently.