British Journal of Anaesthesia, 1981, Vol. 53, No. 12 1337-1345
© 1981 The Board of Management and Trustees of the British Journal of Anaesthesia
research-article |
STEADY-STATE PLASMA FENTANYL IN THE RABBIT*
Department of Anaesthesia, McMaster University 1200 Main Street West, Hamilton, Ontario, Canada L8S 4J9
Present address for correspondence: Centre for Advanced Studies, Division of Health Sciences, Western Australian Institute of Technology, Hayman Road, South Bentley, Western Australia.
Linear pharmacokinetic models were obtained for fentanyl in anaesthetized rabbits. A composite model was used to predict the bolus dose and infusion rates necessary to achieve rapidly a steady-state concentration of fentanyl in plasma. When this was tested in a further six rabbits, steady-state concentrations were greater than predicted. The most likely reasons for this are imperfect mixing between plasma and the central compartment, and substantial uptake of fentanyl by the lung. These sources of error were allowed for in modifications to the model. On further testing, a 4-h infusion set to achieve a plasma fentanyl concentration of 10ng ml–1 yielded actual concentrations ranging from a mean low of 8.7 ng ml–1 to a mean high of 18.0 ng ml–1. The second model described more precisely the disposition of fentanyl, although a tendency to overestimate dosing requirement remained. This tendency is probably a consequence of continuing lung uptake of fentanyl. The demonstrated ability to obtain rapidly and maintain for 4h "steady" blood fentanyl concentrations suggests that the method merits further investigation with other drugs both in animals and man.
*Presented in pan at the 1978 meeting of the Canadian Anaesthetists' Society, the V European Congress of Anesthesiology, Paris, 1978, the 1979 meeting of the American Society for Clinical Pharmacology and Therapeutics (Kansas City) and Australian Society of Anaesthetists, Adelaide, Australia.