How drug-like are 'ugly' drugs: do drug-likeness metrics predict ADME behaviour in humans?
Using a published drug-likeness score based on the calculated physicochemical properties of marketed oral drugs (quantitative estimate of drug-likeness, QED) and published human data, high-scoring and low-scoring drugs were compared to determine how well the score correlated with their actual pharmaceutical and pharmacokinetic (PK) profiles in humans. Drugs with high QED scores exhibit higher absorption and bioavailability, are administered at lower doses and have fewer drug-drug interaction warnings, P-glycoprotein interactions and absorption issues due to a food effect. By contrast, the high-scoring drugs exhibit similar behaviour to low-scoring drugs with respect to free fraction in plasma, extent of gut-wall metabolism, first-pass hepatic extraction, elimination half-life, clearance, volume of distribution and frequency of dosing.
TJR-Chem, Via Alberto 34C, 21020 Ranco, VA, Italy. Electronic address: tim.j.ritchie@gmail.com.
Timothy J
TJ
Ritchie
Respiratory CEDD, GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK. Electronic address: simon.jf.macdonald@gsk.com.
Simon J F
SJ
Macdonald
D000284:Administration, Oral; D001682:Biological Availability; D004347:Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000145:classification / Q000378:metabolism*; D010599:Pharmacokinetics
D004364:Pharmaceutical Preparations