TABLE 1

Studies that used a combination of zero- and first-order kinetics to describe subcutaneous absorption of therapeutic proteins

Model schematic is shown in Fig. 1C.

DrugSpecies/PopulationDuration of the Zero-Order AbsorptionPercentage of Bioavailable Dose Absorbed by Zero-Order ProcessRate Constant for the First-Order AbsorptionBioavailabilitySystemic Disposition ModelReference
AnakinraRat2 hNot reported0.39 h−1100%2CM with linear eliminationLiu et al., 2011
ErythropoietinRat13.5 h680.146 h−159%2CM with linear and MM eliminationWoo et al., 2006
ErythropoietinCynomolgus monkey10 h350.044–0.053 h−1 dose dependent27–100% dose dependent2CM with MM eliminationRamakrishnan et al., 2003
ErythropoietinHealthy humans44–60 h dose dependent880.022 h−10.3884 + 0.0002495 • Dose1CM with MM eliminationRamakrishnan et al., 2004
ErythropoietinHealthy humans0.38–1.39 d dose dependent79.10.7 day−1Not reported1CM with MM eliminationKrzyzanski et al., 2005
FilgrastimHealthy humans6.6 h58.60.403 h−169.1%TMDDWiczling et al., 2009
IL-10aHealthy humans0.47 h5ka1 = 0.16 h−1 with Tlag = 23 h ka2 = 0.61 h−142%2CM with linear eliminationRadwanski et al., 1998
IFN-α2bRabbit1 hNot reported0.1 h−1 Tlag = 3.4 hNot reported3CM with linear eliminationBocci et al., 1986
IFN-α2bHuman patients2.5 h240.18 h−1Not reported1CM with linear eliminationChatelut et al., 1999
Parathyroid hormoneRat5 min70.018 min−1Not modeledHomeostasis model for endogenous hormoneAbraham et al., 2009
  • 1CM, 2CM, 3CM, one-, two-, three-compartment model; IL, interleukin; MM, Michaelis-Menten; TMDD, target-mediated drug disposition.

  • a An additional transit compartment for the first-order process.

  • b Model parameters changed by presence of albumin or hyaluronidase.