A Noninvasive In Vivo Method of Assessing the Kinetics of Halothane Metabolism in Humans

Cahalan, Michael K.; Johnson, Brynte H.; Eger, Edmond I.; Sheiner, Lewis B.; Richardson, C. A.; Varner, Jeffrey K.; Severinghaus, John W.

doi:10.1097/00000542-198210000-00009

Cited by 14 publications

(7 citation statements)

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“…Concentrations of anesthetics in end-tidal gases were measured during washin and for [5][6][7][8][9] days during washout. Concentrations of anesthetics in end-tidal gases were measured during washin and for [5][6][7][8][9] days during washout.…”

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“…Also, when anesthetizing concentrations were used in these studies, only pairs of volatile anesthetics, rather than the full range of those available, were administered simultaneously (5,7,8). When trace concentrations rather than anesthetizing concentrations are applied (6,7), hepatic extraction of anesthetic may increase (9) and therefore play a greater role in elimination of anesthetic.…”

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Pharmacokinetics of Inhaled Anesthetics in Humans

Carpenter

Eger

Johnson

et al. 1986

Anesthesia & Analgesia

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of inhaled anesthetics in humans: measurements during and after the simultaneous administration of enflurane, halothane, isoflurane, methoxyflurane, and nitrous oxide. Anesth Analg 1986;65:575-82.To determine the relative washin and washout characteristics of isoflurane, enflurane, halothane, and methoxyflurane, we administered all four anesthetics simultaneously (total = 1.1 MAC) to nine healthy patients for 2 hr. Concentrations of anesthetics in end-tidal gases were measured during washin and for 5-9 days during washout. Multiexponential (multicompartment) models were fit to the washin and washout curves using least-squares analysis. Slowly equilibrating compartments could only be identified during washout. For 27 of the 36 data sets, five-compartment models fit the washout curves significantly better than four-compartment models. The time constant for our first compartment is consistent with that predicted for washout of the lungs. Time constants for the second, third, and fifth compartments were consistent with current data for blood flows and solubilities of vessel-rich, muscle, and fat tissuegroups, respectively. The fourth compartment has a time constant that lies between the time constants predicted for muscle and fat.

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Pharmacokinetics of Inhaled Anesthetics in Humans

Carpenter

Eger

Johnson

et al. 1986

Anesthesia & Analgesia

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“…2Pulmonary uptake and elimination may vary, depending upon ventilation and perfusion [4]. 3Because of concentration-dependent metabolism, different results may be obtained depending on whether trace concentrations of anaesthetic concentrations are used [11,25,36,37]. (4) Metabolic products from halothane, such as bromide, may be pharmacodynamically active [38,39].…”

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confidence: 99%

Anaesthetic Uptake and Elimination: Is There a Difference Between Halothane and Isoflurane in the Dog?

Zbinden

Thomson

Westenskow

et al. 1988

British Journal of Anaesthesia

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In two groups of dogs, the uptake and elimination of halothane and isoflurane were studied using a closed-loop anaesthetic system which automatically controlled end-tidal halothane and isoflurane partial pressures at equi-MAC concentrations. Haemodynamic and respiratory variables were recorded and the anaesthetic partial pressures were measured in the inspired and expired air, as well as in the arterial, cerebrovenous and mixed venous blood. The controller delivered a higher inspired partial pressure of halothane than of isoflurane to compensate for the higher blood/gas partition coefficient. The partial pressures of halothane in the arterial, cerebrovenous and mixed venous blood increased at rates similar to those of isoflurane. During 160 min of uptake, the cerebral venous partial pressures remained significantly lower than the arterial partial pressures for both agents. On discontinuation of the anaesthetic, the partial pressures of halothane and isoflurane decreased at equal rates in arterial, cerebrovenous and mixed venous blood, and in end-tidal gas. It was concluded that the rate of uptake of isoflurane is more rapid than that of halothane from the alveolar space to the blood, but not from the blood to brain tissue. The rates of elimination from brain tissue and from blood were found to be similar for both agents.

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“…There is a choice of clinically or laboratory derived values of K m and V max for halothane, and both possibilities were explored. Cahalan and co-workers calculated V max to be 6.5 mg min 21 and K m 0.029% from an in vivo study; 7 a later in vitro study identified two oxidative pathways with 8 (these V max values have been scaled up from rates per unit of liver protein to rates per 70 kg human). 9 Values of K m and V max for sevoflurane and enflurane metabolism were obtained by assuming that one mole of fluoride is produced for each mole of anaesthetic metabolized (which may over-estimate, but never underestimate, the extent of anaesthetic biodegradation) and selecting values providing a good fit for clinical fluoride measurements.…”

Section: Methodsmentioning

confidence: 99%