Abstract
Recent studies (D.H. Haynes and A.F. Kirkpatrick, Anesthesiology, 63 (1985) 490–499) have shown that general anesthetic oils such as methoxyflurane (MOF) can be incorporated into lecithin-coated microdroplets of ca. 1000 Å diameter. Intradermal injection of microdroplets of selected general inhalation anesthetics results in reversible local anesthesia. The present study gives information on the time course of absorption, distribution, and elimination of MOF and its metabolites for the intradermal injection of 20 mg of microdroplet-associated MOF in rat tails. Following intradermal injection of MOF microdroplets, the bulk of the injected amount of MOF is absorbed into the blood. The absorption is biphasic with half-times of 2 h and 450 h. The levels of MOF in blood tissue peak within 3 h after injection. The concentrations of MOF metabolites peak 6 h after injection. Studies of the body burden of MOF and its metabolites suggest that the lung is a major elimination pathway, clearing as much as two-thirds of the injected MOF. This is in direct contrast to the fate of MOF administered by inhalation, for which metabolism is the major elimination pathway. With microdroplet administration, the peak levels of MOF in blood and offluoride in plasma are an order of magnitude smaller than the non-effect levels associated with general anesthesia and nephrotoxicity, respectively. This would appear to provide a sufficient margin of safety for any known adverse effect of MOF. The low levels in noninjected tissues are partly attributed to a low dose requirement for local anesthesia and partly to the respiratory-circulatory system which allows a significant amount of MOF to be removed from blood by exhalation before it reaches the other tissues.
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