Mechanistic pharmacokinetic-pharmacodynamic modeling and simulations of naloxone auto-injector 10 mg reversal of opioid-induced respiratory depression.

ABSTRACT: The purpose of the analysis was to evaluate if 10 mg naloxone, administered intramuscularly, could reverse or prevent opioid-induced respiratory depression (OIRD), including OIRD associated with the administration of lethal doses of high-potency opioids. A naloxone population pharmacokinetic (PK) model was generated using data from two naloxone auto-injector (NAI) clinical PK studies. Mechanistic OIRD PK-pharmacodynamic (PD) models were constructed using published data for buprenorphine, morphine, and fentanyl. Due to the lack of published carfentanil data in humans, interspecies allometric scaling methods were used to predict carfentanil PK parameters in humans. A PD model of a combined effect-compartment and receptor kinetics model with a linear relationship between ventilation and carbo

SUBMITTER: Yang TE 

PROVIDER: S-EPMC11494827 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature