No abstract

The purpose of this work was (1) to determine if useful in vivo pharmacokinetic data could be obtained after simultaneous administration of 5-22 compounds of a chemically congeneric series to dogs and (2) to determine if structure-pharmacokinetic relationships could be derived from such studies. Mixtures of structurally related alpha-1 antagonist compounds (5-22) were administered intravenously to conscious dogs. Blood samples were taken over the next 24 h and analyzed by LC/MS to determine plasma levels and pharmacokinetics of each compound. The pharmacokinetics of 17 of these compounds were also determined after individual administration. Results obtained in the N-in-One format for 17 compounds correlated well with results obtained when these same compounds were administered individually. The N-in-One method is a useful method for obtaining pharmacokinetic data on 5-20 molecules in a single animal at one time. The increased throughput in obtaining important pharmacokinetic information should enhance the drug discovery process. In addition, it was possible to determine the extent to which various chemical substitutions did or did not affect pharmacokinetic parameters.

No abstract

No abstract