Drug metabolism and disposition : the biological fate of chemicals
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Drug Metab. Dispos. · Jan 1991
Chronic stress impairs oxidative metabolism and hepatic excretion of model xenobiotic substrates in the rat.
Traumatic injury to both hard and soft tissue has been associated with a decrease in the rate of hepatic drug metabolism. The mechanism(s) underlying this phenomenon have yet to be determined, but may involve substances released from damaged tissues or activation of the adrenocortical axis secondary to stress. ⋯ In addition, the stressed animals evidenced a decreased rate of uptake of indocyanine green by the liver, an apparent decrease in the storage of the dye within the liver, and a decreased hepatic clearance of indocyanine green (presumably due to a decrease in the KM for biliary transport). These observations suggest that atraumatic stress affects several processes involved in the hepatobiliary disposition of xenobiotics.
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Drug Metab. Dispos. · Jan 1991
Dose-dependent stereopharmacokinetics of 5,6-dihydro-4H-4(isobutylamino)thieno(2,3-B)thiopyran-2-sulfonamide-7,7 -dioxide , a potent carbonic anhydrase inhibitor, in rats.
[5,6-dihydro-4H-4(isobutylamino)thieno(2,3-B)thiopyran-2-sul fonamide-7,7- dioxide] (MK-927), a potent carbonic anhydrase inhibitor capable of reducing intraocular pressure after topical application, is currently under investigation for the treatment of glaucoma. The purpose of this study was to characterize the pharmacokinetics of the enantiomers of MK-927 with particular emphasis on the effect of dose on the elimination kinetics. Because the drug resided primarily in erythrocytes, the kinetic analysis was generally performed based on the drug concentration of whole blood. ⋯ Clearly, the magnitude of stereoselectivity in the elimination kinetics of MK-927 enantiomers (40-fold) cannot be explained solely by stereoselective binding. Thus, other factors may also contribute to the overall stereoselectivity in the elimination kinetics of MK-927. The dose-dependent kinetics of the enantiomers was probably due to the saturable binding to carbonic anhydrase.