Inhibition of XXXX 2-hydroxylation by drugs in @entity1 liver microsomes.

@entity1 @entity3659 @entity5829 @entity37454 @entity5080 @entity21946 @entity5957 @entity18457 @entity2644 @entity1406 @entity5127 @entity9956 @entity5126 @entity4807 @entity20611 @entity4591
The 2-hydroxylation of @entity5829 ( @entity9956 ) correlates strongly with the 4-hydroxylation of @entity21946 (D) both in @entity1 volunteers and in vitro comparing @entity1 liver microsomes from different individuals. D competitively inhibits the 2-hydroxylation of @entity9956 in vitro suggesting that @entity9956 is hydroxylated by the ' @entity21946 hydroxylase' which is under monogenic control in @entity1 . We have characterized the effect of drugs on the hydroxylation of @entity9956 in @entity1 liver microsomes by measuring the formation of @entity18457 with HPLC using fluorescence detection. @entity3659 , @entity5080 and @entity1406 inhibited the hydroxylation of @entity9956 competitively indicating interaction with the catalytical site for @entity9956 2-hydroxylation. @entity4591 and @entity20611 at concentrations similar to their Km-values for metabolism did not inhibit @entity9956 -hydroxylation. Thus, for these compounds there was a good correspondence between the drugs' capacity to inhibit @entity9956 2-hydroxylation competitively in vitro and their apparent metabolism by the ' @entity21946 hydroxylase' in vivo in @entity1 . @entity5957 , @entity2644 , @entity5126 and @entity4807 also inhibited @entity9956 -hydroxylation competitively. @entity5957 was an unusually potent inhibitor (apparent inhibition constant Ki = 0.75 microM). @entity5126 was also an unusually potent inhibitor (Ki = 0.27 microM) and much more efficient than its isomer @entity4807 (Ki = 12 microM). Theophylline could inhibit @entity9956 hydroxylation but with atypical kinetics. We suggest that this simple @entity9956 in vitro test as well as earlier described inhibition tests with @entity21946 , @entity5127 and @entity37454 can be used to screen if drugs interact with the ' @entity21946 hydroxylase' in @entity1 liver.
