A survey of clinical pharmacokinetic studies of 17 cardiovascular drugs in Japanese new drug approvals between 2000 and 2007

Abstract

We analyzed the current status of clinical pharmacokinetic (PK) studies in new drug applications (NDA) by evaluating 17 cardiovascular (CV) drugs that were approved between 2000 and 2007 in Japan since CV drugs were one of the largest categories to be submitted. All summaries of data had been submitted by applicants and were freely accessible on the website of the Pharmaceuticals and Medical Devices Agency (PMDA). The clinical PK studies were divided into 12 categories : single-dose, multiple-dose, food-effect elderly, gender difference, mass balance, absolute bioavailability, target patients, liver impairment renal impairment drug-drug interaction, and population PK studies. The median number of clinical PK studies per new molecular entity (NME) excluding single-dose, multiple-dose, and food-effect studies was 13.5, and foreign data accounted for 86% of the study results. A relatively high proportion of PK studies in Japanese subjects were observed in elderly volunteers and target patients ; however, a dependency on foreign data was noted in the other PK study categories. The effect of the guidance "Clinical PK Studies of Pharmaceuticals" by the Ministry of Health, Labour and Welfare on implementation of clinical PK studies could not be fully assessed, since there were only three NMEs approved prior to issuance of the guidance. The median number of clinical PK studies per NME was approximately three times higher for drugs for lifestyle-related diseases than that for other drugs. In recent NDA reviews by the PMDA, the trend to emphasize a relationship between PK and safety with respect to drug-drug interactions and/or special populations was noted.