Pharmacokinetics of XXXX antagonists under development.

@entity1 @entity4444 @entity8 @entity7236 @entity7220 @entity19346 @entity1855 @entity10202 @entity17425 @entity9805 @entity3931 @entity3360 @entity3988 @entity10129 @entity177 @entity3591 @entity460 @entity594 @entity4768 @entity99
@entity460 antagonist drugs under clinical development are of the Type I ( @entity1855 , @entity3988 -like) and Type II ( @entity594 -like) classes. @entity7220 , the only Type I drug currently available, is a high clearance, widely distributed drug which undergoes extensive presystemic elimination. Pharmacokinetically it is quite similar to @entity1855 ; however, it does have increased biliary excretion and decreased binding to plasma proteins. Eight Type II ( @entity7236 ) drugs are reviewed. Seven of these drugs ( @entity10202 , @entity4768 , @entity3360 , @entity17425 , @entity3931 , @entity10129 and @entity9805 ) are pharmacokinetically similar to @entity594 , with high clearance, extensive distribution, and significant presystemic elimination. @entity3591 has lower clearance, even greater peripheral distribution, and greatly decreased presystemic elimination. Three of the 8 @entity19346 have been reported to have plasma protein binding greater than 90%. Unlike @entity594 , each @entity7236 drug under development has an asymmetric centre; therefore each in fact is a racemic mixture. @entity1 pharmacokinetic and pharmacodynamic data have not been reported for any of the racemates. Each of the drugs has been studied in @entity1 with @entity8 . Predictably, @entity1 with severe @entity99 have decreased presystemic clearance and, in some cases decreased clearance after intravenous administration of the @entity19346 , although @entity177 has little influence on their pharmacokinetics. Unfortunately, disease-drug interaction studies of this class of drugs do not generally report plasma protein binding. The effect of age on the disposition of 2 of the @entity19346 has been reported; however, only for @entity3360 can a conclusion be drawn, namely that volume of distribution may increase with age and clearance may remain unchanged. A variety of potential drug-drug interactions have been evaluated, most commonly the effect of these drugs on cardiac glycoside disposition and effect, and the effect of @entity4444 on the disposition of @entity19346 . @entity7220 , like @entity1855 , impairs digoxin clearance significantly. Among the @entity19346 , although minor pharmacokinetic effects have in some cases been reported, the magnitude of the interactions suggest they have limited clinical importance. From drugs currently under development, it is clear that a large number of @entity460 antagonists will soon be introduced into clinical use. Only 1 of the newer drugs, @entity3591 , has significant pharmacokinetic differences from the agents currently in use, although possible pharmacodynamic differences among the drugs have been suggested.(ABSTRACT TRUNCATED AT 400 WORDS)
