Comparisons of Usual Dose of Pharmaceutical Products Used in Japan and United States: Can Differences Be Explained by Pharmacokinetics Alone?

Abstract

Background:

It is important to examine how a usual drug dose is established in Japan and other countries, and to evaluate that on the basis of pharmacokinetic and pharmacodynamic properties. In the present study, we examined the contributions of area under the curve (AUC) ratio and other factors on differences of usual dose between Japan and the United States.

Methods:

We examined drugs approved from January 2008 to January 2011 in Japan and collected related information. For the usual dose set for the same indication in both countries, we compared the maintenance dose values between the countries. We also examined the relationships of AUC ratio and difference of usual dose in both countries.

Results:

Our results clarified that the usual dose for the same indication is comparable between Japan and the United States for 68.75% of the examined drugs, while that for 31.25% is different. Moreover, among products with different approved doses, the dosage was set higher in the United States for 18.75% and higher in Japan for 12.50%. Our findings indicate that the difference in dose between the countries is associated with AUC ratio for 82.1% and by factors other than AUC ratio for 17.9% of the examined medications.

Conclusions:

The approved dose varies between the countries for about one-third of products commonly used. Additionally, it was clarified that not only AUC ratio but also other factors are involved in dosage differences. The present results provide useful information for analysis of factors related to the different usual doses between countries.