Pharmacokinetics and cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys (Macaca mulatta)

Objective - To determine pharmacokinetics and selected cardiopulmonary effe cts of fentanyl in isoflurane-anesthetized rhesus monkeys. Animals - 5 adult male rhesus monkeys. Procedure - Fentanyl (8 mg/kg of body weight, IV) was administered to 6 mon keys anesthetized with isoflurane. End-tidal isoflurane concentration and e sophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after admin istration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory, Results - Heart rate and mean arterial pressure decreased transiently follo wing fentanyl administration. Maximal decreases were observed 5 to 15 minut es after administration. Arterial pH, PaCO2, and PaO2 ranged from 7.46 +/- 0.04 to 7.51 +/- 0.05 units, 29.2 +/- 3 to 34.6 +/- 4.4 mm Hg, and 412.6 +/ - 105.3 to 482.9 +/- 71.2 mm Hg, respectively. The clearance, volume of dis tribution area, volume of distribution steady state, mean residence time, a rea under the curve, elimination rate constant, and half-life were 32.5 +/- 2.48 ml/kg/min, 9.04 +/- 1.91 L/kg, 7.0 +/- 1.2 L/kg, 218.5 +/- 35.5 min, 0.247 +/- 0.019 mg/ml/min, 0.004 +/- 0.001/min, and 192.0 +/- 33.5 min, res pectively. Conclusions and Clinical Relevance - Transient but potentially clinically i mportant decreases in heart rate and mean arterial pressure were observed f ollowing fentanyl administration. Distribution and clearance data were simi lar to those reported for dogs and humans.