The importance of prospective planning of pharmacokinetic trials. Considerations of studies on the phenytoin-digoxin-(P-D) and phenytoin-digitoxin-(P-DT) interaction.

To study possible pharmacokinetic interactions between two compounds a single-dose or a multiple dose experimental design may be used. Two prospective trials on the possible pharmacokinetic interaction between phenytoin (P) and digoxin (D) or digitoxin (DT) were performed in healthy volunteers. It is demonstrated that an statistically significant pharmacokinetic interaction was found only after multiple dosing under conditions of steady-state, whereas after single dosing no interaction was observed. In case of investigating possible pharmacokinetic interactions a multiple dosing trial design appears to be advantageous.