In vitro bioassay as a predictor of in vivo response

Abstract

Background: There is a substantial discrepancy between in vitro and in vivo experiments. The purpose of the present work was development of a theoretical framework to enable improved prediction of in vivo response from in vitro bioassay results.

Results: For dose-response curve reaches a plateau in vitro we demonstrated that the in vivo response has only one maximum. For biphasic patterns of biological response in vitro both the bimodal and biphasic in vivo responses might be observed.

Conclusion: As the main result of this work we have demonstrated that in vivo responses might be predicted from dose-effect curves measured in vitro.

Figure 1

In vivo response for monophasic dose-effect curves measured in vitro. B = 1. a) equation (6), b) equation (7). k_el = 0.0714 1/min, k₁ = 0.0277 1/min, C₀ = 1 nM, γ = β. Illustrative values for fig. 1, 2, 4 taken from Veldhuis et al., (1993) [8] and similar to those measured by Baumann et al., (1987)⁹ for the clearance of growth hormone (GH).

Figure 2

In vivo response for biphasic dose-effect curves measured in vitro. B = 1. a) variation of β, C₀ = 1 nM, b) variation of C₀, β = .388. k_el = 0.0714 1/min, k₁ = 0.0277 1/min, γ = β.

Figure 3

Possible mechanism of bimodal dose-effect curve formation for in vitro systems. a) intermediate z formation as function of x concentration, B₁ = 1, b) final product y formation as function of z concentration, B₂ = 5, c)summary dose-response curve. See comments in the text of the article.

Figure 4

In vivo response for bimodal dose-effect curves measured in vitro. B₁ = 1, B₂ = 5. a) variation of β, C₀ = 1 nM, b) variation of C₀, β = .388. k_el = 0.0714 1/min, k₁ = 0.0277 1/min, γ = β.