The metabolic alteration of drugs.
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The partition of 5,5-dimethyloxazolidine-2,4-dione (DMO) and of 11 amines between the vascular and extravascular spaces of the lung has been determined by the multiple indicator dilution technique. Four amines (nicotine, pentylamine, quinine, and benzylamine) were found to have pH-sensitive tissue to blood concentration ratios. Of these, tritiated nicotine appears to be the nost satisfactory indicator of tissue pH and values for the pH of the pulmonary extravascular space (pH(e)) have been calculated from the nicotine data. At an arterial pH (pH(art)) between 7.38 and 7.43 pH(e) averaged 6.69 +/-0.07. Changes in pH(e) usually paralleled but were consistently less than concomitant changes in pH(art). Alterations in P(CO2) at constant pH(art) regularly produced relatively small, parallel changes in extravascular hydrogen ion concentrations. Local alterations in tissue pH due to P(CO2) changes are apparently buffered quite rapidly and the pH(e) of the lung seems more closely linked to pH(art) than the cellular pH of other tissues.DMO, guanidine, methylamine, morphine, and atropine were confined to the vascular volume during the first circulation and could not be used to measure tissue pH. Histamine appeared to be bound to a pH-insensitive site. The extravascular distributions of antipyrine and aniline were unresponsive to alterations in arterial pH, presumably because they are essentially uncharged at pH levels found in the lung.
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