title: Population pharmacokinetics of intramuscular droperidol in acutely agitated patients.
abstract: Intramuscular 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.
  
  
  
  We undertook a population pharmacokinetic analysis of a subgroup of patients from a clinical trial comparing droperidol and midazolam: 17 receiving 5 mg and 24 receiving 10 mg 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, 5 mg, 10 mg and 10 mg + 10 mg repeated at 15 min.
  
  
  
  A 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 10 h-1provided a stable model and lowest objective function. This represents extremely rapid absorption with a half-life of 5 min. The final model had a clearance of 41.9 l h-1and volume of distribution of the central compartment of, 73.6 l. Median and interquartile range of initial (alpha) half-life was 0.32 h (0.26-0.37 h) and second (beta) half-life was 3.0 h (2.5-3.6 h). Simulations indicate that 10 mg alone provides an 80% probability of being above the lower limit of quantification (5 μg l-1) for 7 h, 2 h longer than for 5 mg. Giving two 10 mg doses increased this duration to 10 h.
  
  
  
  Intramuscular droperidol is rapidly absorbed with high therapeutic concentrations after 5 and 10 mg doses, and supports clinical data in which droperidol sedates rapidly for up to 6 h.
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Lee-Kien
authors.initials: LK
authors.lastname: Foo
authors.affiliation: School of Pharmacy, University of Otago, Dunedin, New Zealand.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Duffull
authors.affiliation: Clinical Toxicology Research Group, University of Newcastle, New South Wales, Australia.
authors.forename: Leonie
authors.initials: L
authors.lastname: Calver
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, New South Wales, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Schneider
authors.affiliation: Clinical Toxicology Research Group, University of Newcastle, New South Wales, Australia.|Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Geoffrey K
authors.initials: GK
authors.lastname: Isbister
mesh_terms: D065567:Absorption, Physiological; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D004329:Droperidol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D008954:Models, Biological; D011237:Predictive Value of Tests; D011595:Psychomotor Agitation / Q000097:blood* / Q000188:drug therapy; D016032:Randomized Controlled Trials as Topic
chemical_list: D014150:Antipsychotic Agents; D004329:Droperidol
keywords: Droperidol; optimal design; pharmacokinetics; population analysis; sedation