Population pharmacokinetics of intramuscular droperidol in acutely agitated patients

作者：Foo Lee Kien; Duffull Stephen B; Calver Leonie; Schneider Jennifer; I**ister Geoffrey K^*

来源：British Journal of Clinical Pharmacology, 2016, 82(6): 1550-1556.

DOI：10.1111/bcp.13093

• Droperidol
• optimal design
• pharmacokinetics
• population analysis
• sedation

BackgroundIntramuscular droperidol is used increasingly for sedation of aggressive and violent patients. This study aimed to characterise the pharmacokinetics of intramuscular droperidol in these patients to determine how rapidly it is absorbed and the expected duration of measurable drug concentrations.
MethodsWe undertook a population pharmacokinetic analysis of a subgroup of patients from a clinical trial comparing droperidol and midazolam: 17 receiving 5mg and 24 receiving 10mg droperidol. Droperidol was measured using high-performance liquid chromatography. Pharmacokinetic modelling was performed under a nonlinear mixed effects modelling framework (NONMEM v7.2). The model was used to simulate concentration time profiles of three typical doses, 5mg, 10mg and 10mg+10mg repeated at 15min.
ResultsA two-compartment first-order input with first-order output model fitted the data best. The absorption rate constant was poorly characterised by the data and an estimate of the first order rate constant of absorption when fixed to 10h(-1) provided a stable model and lowest objective function. This represents extremely rapid absorption with a half-life of 5min. The final model had a clearance of 41.9lh(-1) and volume of distribution of the central compartment of, 73.6l. Median and interquartile range of initial (alpha) half-life was 0.32h (0.26-0.37h) and second (beta) half-life was 3.0h (2.5-3.6h). Simulations indicate that 10mg alone provides an 80% probability of being above the lower limit of quantification (5gl(-1)) for 7h, 2h longer than for 5mg. Giving two 10mg doses increased this duration to 10h.
ConclusionsIntramuscular droperidol is rapidly absorbed with high therapeutic concentrations after 5 and 10mg doses, and supports clinical data in which droperidol sedates rapidly for up to 6h.

• 出版日期2016-12