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

Abstract

Objective - To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys. Animals - 6 adult male rhesus monkeys. Procedure - Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal 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 administration 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 following fentanyl administration. Maximal decreases were observed 5 to 15 minutes 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 distribution area, volume of distribution steady state, mean residence time, area 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, respectively. Conclusions and Clinical Relevance - Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans.