Alfentanil's Analgesic, Respiratory, and Cardiovascular Actions in Relation to Dose and Plasma Concentration in Unanesthetized Dogs

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Abstract
Relationships between plasma concentrations of alfentanil and its analgesic, respiratory, and cardiovascular effects were determined in dogs. To avoid drug interaction, trained, unanesthetized, spontaneously breathing dogs were used. After a control period in the awake state, alfentanil was injected in increasing amounts (10, 20, 80, 160, and 320 .mu.g/kg) at 5-min intervals to a total dose of 590 .mu.g/kg administered over 20 min. The effects were observed on pain responses (heart rate and blood pressure changes and somatic reactions to tail clamping), respiration (respiratory rate, oxygen consumption [.ovrhdot.VO2], blood gas tensions) and circulation (heart rate and blood pressure). The plasma concentration-effect curves, derived by relating the changes in multiple variables from the awake state to the corresponding plasma concentrations (range 8-5079 ng/ml), plateaued at and around 200 ng/ml during the injection period but were displaced in parallel to two-fold higher concentrations during recovery, which resembles acute tolerance. At maximmaly effective analgesic concentrations, which precipitated profound cardiorespiratory slowing with conspicuous hypoxemia, the .ovrhdot.VO2 of 4.4 .+-. 0.3 ml .cntdot. kg-1 min-1 corresponded with the calculated metabolic rate but increased to 6.3 .+-. 1.6 ml .cntdot. kg-1 during recovery. The analgesic action of alfentanil, which cannot be separated from its depressant cardiorespiratory effects and maximally effective analgesic concentrations (between 200 and 400 ng/ml), apparently does not jeopardize the adequacy of tissue oxygenation in dogs.