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The Influence of Hepatic Plasma Flow on Alfentanil Plasma Concentration Plateaus Achieved with an Infusion Model in Humans

Measurement of Alfentanil Hepatic Extraction Coefficient

Department of Anesthesiology, Hôpital de la Pitié, Paris, France

Abstract

In a group of seven patients undergoing intracranial surgery under neurolept anesthesia, an alfentanil infusion was initiated with a loading dose of 235 µg/kg over 5min, followed by a maintenance infusion rate of 1.8 µg/kg^–1·min^–1 in order to obtain a steady state plasma concentration (C_ss) of 400 ng/ml^–1 according to an infusion model. The mean values of C_ss (446 ± 209 ng/ml) were close to the predicted ones. Nevertheless, an important intersubject variability in C_ss values was observed. A positive linear correlation existed between alfentanil steady state clearance and indocyanine green clearance (r = 0.88) and between alfentanil steady state clearance and cardiac index (r = 0.93). In three patients, a catheter was inserted into an hepatic vein to determine the alfentanil hepatic extraction coefficient. Alfentanil plasma clearance did not differ from alfentanil hepatic clearance and alfentanil hepatic extraction coefficient values ranged from 0.32–0.53. We conclude that alfentanil is a drug with an intermediate hepatic extraction coefficient and that alfentanil plasma clearance depends on hepatic plasma flow, which is thus one of the factors accounting for individual variability in plasma concentration plateaus achieved with an infusion model.

Key Words: ANALGESICS—alfentanil • ANESTHETICS, INTRAVENOUS—alfentanil • PHARMACOKINETICS—alfentanil

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999