Translating biologics PK from preclinical species to humans

Clients often need to translate biologics PK from preclinical species to humans. The right method depends on the modeling needs of the program.

If full PBPK is required, for mAbs the standard in my practice remains the Shah & Betts PBPK [1] or the Jones et al. paper [2]. More broadly, anything from Shah's lab over the past 15+ years is gold for understanding biologics distribution. For translation, you can take the rates and volumes from the original papers, calibrate against available data, and apply allometric scaling to translate to human.

When a full PBPK model is overkill, several minimal PBPK models can be applied depending on the situation — [3], [4], [5] (and many others!). These models offer the advantage of physiological detail, but the disadvantage is that they don't easily convert to a typical two-compartment framework — which can limit intuition when discussing with a classically trained pharmacometrician.

Sometimes you only care about what happens in a specific organ. In that case, an ultra-minimal PBPK model focused on the site of action may be preferred. I was fortunate to be involved in publishing two such models — SoA [6] and piPK [7]. These still describe the compartment of interest physiologically, while using parameters from classical two-compartment PK models.

For the classical two-compartment model itself, standard allometric scaling applies — Betts et al. is a useful reference here: [8].

The right approach depends heavily on your program's specific needs.

What am I missing? Do you have a go-to method or publication for this?

References in the first comment below 👇

#QSP #Pharmacometrics #PBPK #DrugDevelopment #Biologics

De-risk your drug development strategy through mechanistic modeling. Learn more at pharmath.io.

References:

[1] Shah DK, Betts AM. J Pharmacokinet Pharmacodyn. 2012. doi: 10.1007/s10928-011-9232-2

[2] Jones HM et al. CPT Pharmacometrics Syst Pharmacol. 2019. doi: 10.1002/psp4.12461

[3] Cao et al. J Pharmacokinet Pharmacodyn. 2013. doi: 10.1007/s10928-013-9332-2

[4] Bloomingdale P et al. J Pharmacokinet Pharmacodyn. 2021. doi: 10.1007/s10928-021-09776-7

[5] Spinosa P et al. CPT Pharmacometrics Syst Pharmacol. 2026. doi: 10.1002/psp4.70167

[6] Kapitanov GI et al. Front Bioinform. 2021. doi: 10.3389/fbinf.2021.731340

[7] Kapitanov GI et al. CPT Pharmacometrics Syst Pharmacol. 2026. doi: 10.1002/psp4.70160

[8] Betts A et al. MAbs. 2018. doi: 10.1080/19420862.2018.1462429.