Inclusion of human intravenous study data in new drug applications-impact of the Japanese guidance.

Human pharmacokinetic study after intravenous (i.v.) administration is inevitable in calculating basic pharmacokinetic parameters such as bioavailability, clearance, and distribution volume. However, i.v. data are not always included in the dossier, although the regulatory guidance recommends the inclusion of i.v. studies for Japanese new drug applications. We investigated the adherence to this guidance on the inclusion of i.v. data along with various factors. Logistic regression analyses were carried out on 117 new oral drugs approved in Japan between 1999 and 2009. Inclusion of i.v. data conspicuously increased after the issuance of the guidance for self-originated drugs developed by Japanese firms [odds ratio (OR) = 30-41). Moreover, drugs exhibiting large interindividual variations in pharmacokinetics showed a positive association (OR = 4.1-8.2), whereas solubility did not show notable association (OR = 1.0) with inclusion of i.v. data. Inclusion of i.v. data was not associated with physicochemical feasibility, but the developer's willingness to comply with the guidance seems to be involved.