Previous in vivo studies have suggested that phenobarbitone increases the first pass clearance of norethindrone in the rat by induction of enzymes both in the gut wall and liver. In the present study phenobarbitone caused an increase in both the production of highly polar ether-extractable metabolites and the conjugation of the steroid as it crossed the wall of the everted gut sac preparation. In addition, there was a marked increase in the uptake of norethindrone into the liver followed by increased phase I metabolism in the isolated perfused liver. As expected for a highly cleared drug, enzyme induction had no measurable effect on the terminal half-life of norethindrone in the perfused liver preparation.
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