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TGA Pfizer document from January 2021 24th March 2023 (sorry) Tissue distribution (lipid nanoparticles encapsulation RNA) (Page 44) Rats after i.m. vaccine injection The concentration of radioactive lipid marker reached the peak level in plasma (8.9 μg lipid eqv/mL), between 1 – 4 h post-dose, and distribution mainly into liver, adrenal glands, spleen and ovaries over 48 h Concentrations were higher in plasma than in blood, with mean blood: plasma ratios of 0.5 – 0.6. DISTRIBUTION (page 40) The distribution of LNP-BNT162b2 (V9) mRNA or expressed S protein was not studied. Table 4-2. Mean concentration of radioactivity (sexes combined) in tissue and blood following a single IM dose of 50 μg mRNA/rat (page 45) Mean total radioactivity was greatest at the injection site followed by the liver, with much lower total recovery in spleen, adrenal glands and ovaries The tissue distribution pattern was similar in 100 μg mRNA/animal dose group as noted above for 50 μg mRNA/animal dose, with highest distribution into liver, adrenal glands and spleen. Conclusions Slow but significant distribution of lipid nanoparticles from the site of injection with major uptake into liver. Minor distribution in spleen, adrenal glands and ovaries over 48 h. Mean blood:plasma ratios of indicating nanoparticles mainly present in plasma fraction of blood with peak concentrations in plasma at approx. 2 h post-dose. Liver concentrations over time 25 mins 1 hour 2 hours 4 hours 8 hours 24 hours 48 hours METABOLISM (page 46) In vitro studies indicated minor metabolism of ALC-0159 and ALC-0315 in liver, with most of the lipids found unchanged at the end of the 2 or 4 h incubation period
