In the late 1980s, the French military developed a water-soluble version of diazepam, avizafone (AVF), to use in a three-drug cocktail in combination with atropine and pralidoxime that was intended to be placed in an autoinjector for battlefield delivery of an antidote to nerve gas poisoning. Other drawbacks of intramuscular (IM) or IV administration of commercial diazepam are: significant irritation and pain at the injection site, inability to add other pre-operation drugs to the same syringe due to risk of precipitation, inability to deliver the diazepam from an IV bag, inability to administer subcutaneously (SQ), and slow and erratic absorption of the drug upon IM injection due to the variability in fat content among patients. It is recommended that a large vein should be used. When administered intravenously (IV), the commercial drug product requires a slow bolus (30 sec/mL) to prevent the drug from coming out of solution or causing significant irritation of the vein. Per the package insert of the commercial drug product, to solubilize diazepam in a solution of sufficient concentration to be acceptable for a parenteral product, it is dissolved in a solution that is 40% propylene glycol, 10% ethyl alcohol, and 5% benzyl alcohol. One of the drawbacks of diazepam is that it is very poorly soluble in water. The concentration of diazepam in the currently available commercial product is 0.0176 M. It is also a useful premedication for relief of anxiety and tension in patients who are scheduled to undergo surgical procedures. Diazepam is a useful adjunct in status epilepticus and severe recurrent convulsive seizures. Diazepam is also a useful adjunct for the relief of skeletal muscle spasm due to reflex spasm to local pathology, such as inflammation of the muscles or joints, or secondary to trauma. In a patient experiencing acute alcohol withdrawal, diazepam may be useful in the symptomatic relief of acute agitation, tremor, impending or acute delirium tremens, and hallucinations. Description of the Related Artĭiazepam is a medication that is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety. The present disclosure relates generally to the field of pharmaceutical therapeutics, and more specifically to the administration of compounds capable of sedation, including compounds for the sedation of COVID patients. 63/031,155 filed May 28, 2020, which is incorporated herein by reference. Once finished in PKPlus, the parameter values of the selected model can be easily transferred back to the main GastroPlus model, and report-quality outputs can be captured and saved.This application claims the benefit of U.S. Residual information is also captured and can be plotted. Linear or saturable clearance models can be easily selected.įull statistics, including Akaike Information Criterion and R^2, are provided for all models. time profiles – IV, oral, or combination of IV and oral as well as different dose levels. Compartmental PK models can be fitted to single IV or oral data as well as across multiple plasma concentration vs. time profiles, dose, body weight and infusion time (if applicable). Required inputs are plasma concentration vs. The fitted parameters include PK properties, first order absorption rate, bioavailability and absorption lag time (if both IV and oral data are included in fitting). The optimization and selection of the appropriate compartmental PK model is automated from a single mouse click, but you control which parameters are transferred back to the main GastroPlus model.
#Winnonlin 2 compartment full#
The PKPlus™ Module extends GastroPlus ® to rapidly estimate pharmacokinetic (PK) parameters for noncompartmental analysis (NCA), along with 1-, 2-, & 3-compartment PK models from pharmacokinetic studies (IV and/or oral) without the need to run full simulations.