Fig. 4.

PK–PD modeling of anti-lipolytic effects of Adenosine A1 receptor agonists in rats: prediction of tissue-dependent efficacy in vivo. a Relationship between intrinsic efficacy in an in vitro (GTP-shift) and in vivo (log τ) bioassay for the effect of a series of A1 receptor agonists on heart rate and lipolysis (as measured by nonesterified fatty acids, NEFAs), respectively. The difference in the intercept for the two effects is explained by the difference in receptor density between adipose tissue and cardiac tissue. b Relationship between intrinsic efficacy in an in vitro bioassay (GTP shift) and in vivo intrinsic activity (α) for the effects on heart rate and lipolysis, respectively. The graphs show that partial agonists with GTP shift values between 1 and 5 display the highest selectivity of action for the effect lipolysis versus heart rate. Reproduced from van der Graaf et al. [70]