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Published on: April 17, 2013
Size-dependent renal filtration model explains human pharmacokinetics of a functional nanoparticle: The SPAGOPIX-01
Oskar Axelsson1, Nooshin Yousefpour1, Olof Björnberg1
1Spago Nanomedical AB, Scheelevägen 22, SE-223 63 Lund, Sweden.
Abstract:
The pharmacokinetics in patients dosed with the nanoparticle-based MRI contrast agent SN132D is explained by a size dependent clearance mechanism and this behavior was modeled numerically. Blood samples from 14 patients were analyzed for silicon (a component of the nanoparticle) by ICP-OES. The pharmacokinetic model has only one free parameter and relies on a measured size distribution of the contrast agent and well-established properties of the renal and cardiovascular systems. The model fits well (R2 = 0.9910) with experimental data from samples taken from ten minutes to two weeks after start of infusion. These results support that the cut-off diameter for human renal filtration is 5.5 nm. The agreement between experiment and model implies that there is little or no plasma protein binding to the nanoparticles.
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