Effects of Intramuscular Vasopressin on Pharmacokinetics and Pharmacodynamics in Healthy Neonatal Piglets: A Dose-Response Study

肌注血管加压素对健康新生仔猪药代动力学和药效学的影响:剂量反应研究

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Abstract

BACKGROUND: Neonatal resuscitation guidelines recommend the use of the vasopressor epinephrine during neonatal cardiopulmonary resuscitation (CPR); however, vasopressin may be a potential alternative. Successful neonatal CPR requires rapid vasopressor administration, but the current guideline-recommended routes can take several minutes to establish and require substantial skill and/or training. The intramuscular (IM) route provides rapid drug administration and does not require special skills, training, or equipment. OBJECTIVE: We aimed to compare two doses of IM vasopressin to intravenous (IV) vasopressin in a healthy neonatal piglet model to examine the hemodynamic and pharmacokinetic effects. METHODS: Fifteen neonatal piglets (n = 5/group; 1-3 days of age) were anesthetized, intubated via a tracheostomy, and randomized to 4 IU/kg IM vasopressin, 8 IU/kg IM vasopressin, or 0.4 IU/kg IV vasopressin. Various hemodynamic and cardiac function parameters were continuously recorded throughout the experiment. Blood was collected prior to drug administration and throughout the experiment for pharmacokinetic and pharmacodynamic analysis. RESULTS: The 4 IU/kg IM vasopressin dose was ineffective in producing systemic changes in hemodynamics or cardiac function as it was poorly absorbed. The 8 IU/kg IM vasopressin dose had comparable results to IV vasopressin and was rapidly distributed to systemic circulation. CONCLUSIONS: The higher IM vasopressin dose of 8 IU/kg is effective in increasing systolic and diastolic blood pressure.

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