The Uptake and Distribution of Four Inhalation Anesthetics in Dogs

Pharmacokinetics of Drug Disposition: Hemodynamic Considerations

“…Ex pressed somewhat differently, effluent blood from an organ and the tissue may be regarded as being in equilibrium with respect to the diffusible drug moiety. Those drugs whose disposition has been modeled-anesthetic gases (16,18,19,(40)(41)(42)(43), thiopental (13, 14,116,117), propranolol (118), ethanol (119), lidocaine (32), 1-/3-D-arabinofuranosylcytosine (120), and methotrexate (36,37,87,(121)(122)(123) -are fairly lipid-soluble and therefore this assumption is probably valid, at least for the major organs. However, in the case of methotrexate, the transport of drug from the blood into the bone marrow, spleen, and small intestine is much slower than the rate of tissue perfusion and thus signifi cant membrane resistance exists (123).…”

“…On the other hand, little information is usually available on the kinetics of drug binding to tissue constituents, particularly over a wide concentration range. In general, linear binding has been assumed for the anesthetic gases (16,18,19,(40)(41)(42)(43), thiopental (13, 14), lidocaine (32), ethanol (119), and 1-/3-D-arabinofuranosylcytosine (120) based upon experi mentally determined blood/tissue equilibrium concentration ratios generally ob tained after a single acute dose of the drug. Initially, linear tissue binding was assumed for methotrexate (121) but further studies (87,123) indicated the presence of a specific binding site in certain tissues that dominated uptake at low plasma concentrations.…”

“…The importance of perfusion on the alveolar uptake and cerebral distribution of a number of anesthetic gases has been well demonstrated by simulations (J 6,18,19). Increased perfusion of the pulmonary tissue by increasing the cardiac output leads to an enhanced uptake of anesthetic into the sytemic circulation, whereas lowering the output has the opposite effect, the changes being most pronounced with those gases exhibiting the greatest solubility in the blood.…”

Control of industrial exposure to tetrachloroethylene by measuring alveolar concentrations: theoretical approach using a mathematical model

“…Borgstedt, and Gillies (1972). In our model, we had to assume that the tissue-blood partition coefficient for adipose tissue was the same as that for trichloroethylene.…”

“…The assumptions on which such a mathematical model is based have been discussed by several authors (Eger, 1963a;Mapleson, 1963;Kety, 1951;Cowles et al, 1972). The main assumptions are: (a) there is no limitation of diffusion between alveolar gas and pulmonary blood or between peripheral blood and tissue groups, and equilibrium is reached almost instantaneously; (b) alveolar ventilation, rates of blood flow, and other physiological or physical parameters are constant unless stated otherwise; (c) concentration within each compartment, particularly within each tissue group, is uniform; (d) there is no diffusion ofsolvent between tissue groups; (e) there are neither unventilated alveoli nor arteriovenous shunts; (f) the respiratory quotient is 1.…”