Novel methods for the assessment of safety pharmacology and toxicology parameters in anesthetized and ventilated dogs receiving inhaled drugs

Publication date: Available online 9 May 2019Source: Journal of Pharmacological and Toxicological MethodsAuthor(s): K. Bujold, J. Pfeiffer, J. Fink, R. Malcolmson, S. Authier, J. TepperAbstractIntroductionFor nonclinical drug development, it is optimal if safety pharmacology and toxicology studies are performed in a model that reasonably represents the patient the drug is intended to treat. To simulate prolonged inhalation therapy in ventilated patients, GLP inhalation toxicology methods, including safety pharmacology endpoints, in anesthetized, intubated and mechanically ventilated dogs were developed. This model required establishment of a canine intensive care unit (ICU) capable of providing prolonged anesthesia (propofol infusion and morphine titration) and partial parenteral nutrition (dextrose, amino acids and lipids) while safety parameters were monitored.MethodTelemetry was used to continuously monitor heart rate, ECG and blood pressure. Blood gas parameters were periodically measured while oxygen saturation and core temperature were reported continuously. Glucose was measured hourly while other standard clinical pathology (hematology, coagulation, clinical chemistry) samples were evaluated approximately every 12 h. Aerosols were administered continuously over 48 h by inhalation using a mesh nebulizer (Aerogen Solo) fed by a syringe pump into a humidified circuit of a critical care ventilator (LTV® 1000) ending in an endotracheal tube placed in the trachea. Anima...
Source: Journal of Pharmacological and Toxicological Methods - Category: Drugs & Pharmacology Source Type: research