Fig 1.
Biodistribution study: Concentration-time course of rHuPH20 in skin samples after ID delivery.
rHuPH20 concentration in skin samples from individual animals (circles) are depicted as well as the mean (line) for each time point. (A) Concentration in U/mL, LLOQ = 0.70 U/mL. (B) Concentration in U/mg wet tissue weight, LLOQ = 0.02 U/mg, *P<0.05; two-tailed t-test; samples beyond 15 minutes compared with samples at 1 and 15 minutes. Values lower than the LLOQ (shaded area) are plotted as 0. LOQ, lower limit of quantitation; rHuPH20, recombinant human hyaluronidase PH20.
Fig 2.
Biodistribution study: Concentration-time course of rHuPH20 in lymph samples after ID delivery.
rHuPH20 concentration in lymph samples from individual animals (circles) are depicted as well as the mean (line) for each time point. (A) Concentrations in U/mL, LLOQ = 0.70 U/mL. (B) Concentrations in U/mg wet tissue weight, LLOQ = 0.02 U/mg. Values lower than the LLOQ (shaded area) are plotted as 0. ID, intradermal; LLOQ, lower limit of quantitation; rHuPH20, recombinant human hyaluronidase PH20.
Fig 3.
Biodistribution study: Concentration-time course of rHuPH20 in plasma samples after ID delivery.
rHuPH20 concentration (U/mL) in plasma samples from individual animals (filled circles) are depicted as well as the mean (line) for each time point. Values lower than the LLOQ (<0.3 U/mL; shaded area) are plotted as 0. The outlier value in parentheses is suspected to have resulted from partial injection of rHuPH20 into the blood compartment and was therefore omitted from the statistical calculations. ID, intradermal; LLOQ, lower limit of quantitation; rHuPH20, recombinant human hyaluronidase PH20.
Fig 4.
Concentration-time course of rHuPH20 in plasma samples following IV administration.
rHuPH20 concentration (U/mL) in plasma samples from individual animals (filled circles) are depicted as well as the mean (line) for each time point. Values lower than the LLOQ (<0.3 U/mL; shaded area) are plotted as 0. IV, intravenous; rHuPH20, recombinant human hyaluronidase PH20; LLOQ, lower limit of quantitation.
Fig 5.
Dye dispersion assay validation: Effect of ascending systemically administered doses of rHuPH20 on intradermal dye dispersion.
Measurement of dispersion area (A) 5 minutes and (B) 15 minutes post-dye injection in the skin. Each point represents the mean of duplicate measurements from one animal; the bar represents the mean for all animals. Asterisk denotes statistical significance of P<0.05 versus control. IV, intravenously; rHuPH20, recombinant human hyaluronidase PH20.
Fig 6.
Dye dispersion: Characterization of dispersive effects at a distal site after ascending intradermal rHuPH20 dose administration at a contralateral skin site.
Measurement of dye dispersion area (A) 5 minutes and (B) 15 minutes post-dye injection. Each point represents the mean of duplicate measurements from one animal; the bar represents the mean for all animals. ID, intradermally; rHuPH20, recombinant human hyaluronidase PH20.