Isoflurane pharmacokinetics

Several general anesthetics (isoflurane, ketamine, thiopental, etomidate) have one or more chiral carbons and thus exist as pairs ot stereoisomers. In many cases one stereoisomer is more potent than the other at providing anesthesia despite little difference in pharmacokinetics (Christensen Lee, 1973 Benthuysen et ak, 1989 Harris et ak, 1992 Dickinson et ak, 1994). The stereoisomers have equal hydrophobic properties and partition equally into the membrane. 

Cooper RA, Maddineni VR, Mirakhur RK, Wierda JM, Brady M, Fitzpatrick KT. Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure. Br J Anaesth 1993 71(2) 222-6. 

A. Classification and Pharmacokinetics The agents currently used in inhalation anesthesia are nitrous oxide (a gas) and several easily vaporized liquid halogenated hydrocarbons, including halothane, desflurane. enflurane, isoflurane, sevoflurane, and methoxyflurane. They are administered as gases their partial pressure, or tension, in the inhaled air or in blood or other tissue is a measure of them concentration. Since the standard pressure of the total inhaled mixture is atmospheric pressure (760 mm Hg at sea level), the partial pressure may also be expressed as a percentage. Thus 50% nitrous oxide in the inhaled air would have a partial pressure of 380 mm Hg. The speed of induetion of anesthetic effects depends on several factors ... 

Several studies have similarly found that the use of esmolol reduced the required dose of isoflurane or propofol, or resulted in a deeper anaesthesia (as measured by BIS), but only in the presence of an opioid. " As there appears to be no pharmacokinetic interaction between esmolol and propofol it has been suggested that esmolol could be interacting with the opioid. ... 

Khan ZP, Munday IT, Jones RIvL Thornton C, Ivfent TG, Amin D. Effects of dexmedetomidine on isoflurane requirements in healdiy volunteers. 1 Pharmacodynamic and pharmacokinetic interactions, Br JAnaesth (1999) 83, 372-80. 

Limited evidence suggests parecoxib does not affect the pharmacokinetics or clinical effects of propofol. Parecoxib does not appear to interact with nitrous oxide and isoflurane. 

In vivo F MRS has also been used to study the pharmacokinetics and metabolism of anaesthetic agents such as halothane, isoflurane and desflurane in experimental animals. It has also been shown that anaesthetic agents can be observed noninvasively in the brains of patients immediately following surgery. The principal aim of these studies was to elucidate the mechanism of action of these compounds and eventually help in the development of more effective and selective anaesthetics. Unfortunately, factors such as sensitivity and localization of the region of interest (which are particularly relevant to the study of anaesthetics) have greatly limited the impact of this research. 

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