Ethnic comparability of safety and pharmacokinetics of florbetaben (BAY 94-9172) in normal Caucasian and Asian subjects

Objectives As 18F-florbetaben is in current global development as a PET tracer for detection of cerebral beta-amyloid deposition, it is important to investigate the pharmacokinetics in different ethnic groups at an early developmental phase.

Methods Two identical phase I trials were performed for German and Japanese healthy volunteers, each in 18 subjects, to evaluate the pharmacokinetics and safety of a single dose of 300MBq 18F-florbetaben, either of low(≤ 5µg, LD) or high (50-55µg, HD) mass dose. Pharmacokinetic parameters were evaluated based on the total 18F-radioactivity in plasma followed by metabolite analysis using radio-HPLC.

Results Pharmacokinetics of unchanged plasma 18F-florbetaben were characterized by a rapid elimination. The dose-normalized area-under-curve of the unchanged plasma compound as an indicator of the input to the brain were comparable between LD and HD as well as between Germans (LD: 0.38min/L, HD: 0.55min/L) and Japanese (LD: 0.35min/L, HD: 0.45min/L) without significant difference, suggesting ethnic comparability and dose proportionality in florbetaben pharmacokinetics of up to the high mass dose. A polar metabolite fraction consisting presumably of several components was the main radiolabeled degradation products in the plasma radioactivity, and was also comparable between the doses and the ethnic groups. Approximately 35% of the administered radioactivity was excreted to urine up to 12 h post injection and almost all the radioactivity in the urine was presented by the polar metabolites. The most frequent adverse effects were general disorders and administration-site conditions, and no signs of compound-related safety concern were observed.

Conclusions Overall, there were no significant differences in the pharmacokinetics of 18F-florbetaben in Germans and Japanese which warrants further global development of the tracer.

Research Support Bayer Healthcar