Table 3. Some in vitro assays for pharmacokinetic/ADME properties.
Property | Assays |
---|---|
Chemical and physical properties | In silico predictions or in vitro measurements of logP (Mannhold et al, 2009), logD (Bruneau and McElroy, 2006; Dohta et al, 2007), pKa (Lee et al, 2007) and solubility (Colclough et al, 2008; Du-Cuny et al, 2008) |
Metabolism | Mouse, rat, human liver microsomes, hepatocytes, S9 incubations, UGT assays (Houston and Carlile, 1997; Riley et al, 2002) |
Passive diffusion/cell uptake | PAMPA (Ottaviani et al, 2006) |
Cell and gut permeability predictions | Caco-2 cells (Artursson et al, 2001) |
Blood–brain barrier permeability predictions | hCMEC/D3 cells (Poller et al, 2008) |
Drug–drug interactions (e.g., CYP450) | Human liver microsomes, hepatocytes, CYP enzyme screens (Masimirembwa et al, 2001) |
Protein binding | Measurement by dialysis or ultrafiltration (Howard et al, 2010) |
Abbreviations: ADME=absorption, distribution, metabolism and elimination; CYP450=cytochrome-P450; PAMPA=parallel artificial membrane permeability assay; UGT=uridine diphospho (UDP)-glucuronosyltransferase.