Humans are animals, but are animals human enough? A systematic review and meta-analysis on interspecies differences in renal drug clearance

Various animal models are used to study pharmacokinetics (PK) of drugs in development. Human renal clearance (CLr) should be predictable through interpolation from animal data by allometric scaling. Based on this premise, we quantified interspecies differences in CLr, and related them to drug properties. Using PubMed and EMBASE, we systematically reviewed literature on human and animal CLr measures for 20 renally excreted drugs, calculated average fold errors, and quantified mean differences between animals and humans. Our results show that animal models are generally good predictors for human drug clearance using simple allometry, except for rats, with which human CLr is significantly overestimated.