Kaufman R D, Aqleh K A, Bellville J W
J Pharmacol Exp Ther. 1979 Jan;208(1):73-9.
Fentanyl, 0.7 and 1.4 microgram/kg, alphaprodine, 0.135 and 0.270 mg/kg meperidine, 0.564 and 1.127 mg/kg, and placebo were administered intravenously over 2.6 min by infusion to five healthy adult males. The crossover study was of incomplete Latin square design with at least 1 week between administrations of each study drug. The subjects breathed from a mixing chamber the gas composition of which was servo-controlled so as to produce CO2 ramps in the end-tidal gases. Each experiment was composed of: 1) control CO2 ramps, 2) a 25-min isocarbic run during which the drug was infused and 3) CO2 ramps at half-hour intervals for 3 hr postinfusion. The 20-liter intercept (the PETCO2 at which ventilation was 20 liters/min) was used as the measure of respiratory drive; the change in 20-liter intercept measured drug effect. The potency ratios at peak effect were: fentanyl/meperidine, 679; alphaprodine/meperidine, 3.68; fentanyl/alphaprodine, 179. With the area under the time-effect curves, the potency ratios of mean effect were: fentanyl/meperidine, 45c; alphaprodine/meperidine, 3.00; fentanyl/alphaprodine, 141. Thus, both fentanyl and alphaprodine are shorter-acting than meperidine, and fentanyl is shorter-acting than alphaprodine. The time-effect curves were fitted to linear and mono- and bi-exponential models. The time constants were compatible with the above relative durations of action.
将0.7微克/千克和1.4微克/千克的芬太尼、0.135毫克/千克和0.270毫克/千克的阿法罗定、0.564毫克/千克和1.127毫克/千克的哌替啶以及安慰剂通过静脉输注在2.6分钟内给予5名健康成年男性。该交叉研究采用不完全拉丁方设计，每种研究药物给药之间至少间隔1周。受试者从一个混合室呼吸，混合室的气体成分由伺服控制，以便在呼气末气体中产生二氧化碳斜坡。每个实验包括：1）对照二氧化碳斜坡；2）25分钟的等碳酸运行，在此期间输注药物；3）输注后3小时每隔半小时进行二氧化碳斜坡。将20升截距（通气量为20升/分钟时的呼气末二氧化碳分压）用作呼吸驱动力的指标；20升截距的变化测量药物效应。峰值效应时的效价比为：芬太尼/哌替啶，679；阿法罗定/哌替啶，3.68；芬太尼/阿法罗定，179。根据时间-效应曲线下的面积，平均效应的效价比为：芬太尼/哌替啶，45；阿法罗定/哌替啶，3.00；芬太尼/阿法罗定，141。因此，芬太尼和阿法罗定的作用时间均比哌替啶短，且芬太尼的作用时间比阿法罗定短。时间-效应曲线拟合为线性、单指数和双指数模型。时间常数与上述相对作用持续时间相符。
