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Soluble Receptor Half-Life

Soluble forms of many receptors (cleaved extracellular domains or secreted truncated forms) can be detected in the circulation. Such soluble receptors can possess important biological activity and therefore serve as a target of interest or simply serve as a competitive binding partner of the drug. In the latter case, soluble receptors act as a sink, preventing the drug from binding to the membrane bound form of the receptor.

The half-life, \(T_{1/2, sR}\), defines the elimination rate of the soluble receptor. In Assess models, this parameter, along with steady-state concentrations, are used to calculate the synthesis rate of the soluble receptors. Assess models apply the simplifying assumption that elimination occurs at the same half-life in all compartments.

Soluble Receptor Half-Life in Assess

Soluble receptor half-life is best identified from measured clearance (plasma pharmacokinetics) of exogenously administered soluble receptor. Data from preclinical animal models can be converted to human-specific values through allometric scaling.

In the absence of data, a reasonable estimate range of values may be obtained using comparators with a similar molecular weight.

Common search terms for finding soluble receptor half-life in literature include:

  • Circulating half-life
  • Turnover
  • Plasma clearance

Allometric Scaling

Soluble half-life in humans may be estimated by allometrically scaling the clearance from other species. For example, the pharmacokinetics of IV administered recombinant soluble IL-4R, radiolabelled with 125I, was characterized in mice by Jacobs et al. (Figure 6). The elimination half-life was reported to be 2.3 hr (Table 1). This can be allometrically scaled to humans, using the equation:

\[ \frac{T_{1/2 species_1}}{T_{1/2, species_2}} = \left( \frac{BW_{species_1}}{BW_{species_2}} \right)^{0.25} \]

The resulting estimate in humans would be about 18 hr.


  • Jacobs CA, Lynch DH, Roux ER, Miller R, Davis B, Widmer MB, Wignall J, VandenBos T, Park LS, Beckmann MP. Characterization and pharmacokinetic parameters of recombinant soluble interleukin-4 receptor. Blood. 1991 Jun 1;77( 11): 2396-403. PMID: 2039820.