Prediction of human renal clearance from preclinical species for a diverse set of drugs that exhibit both active secretion and net re- absorption

Abstract

Number of words in abstract: 184 Number of words in introduction: 552 Number of words in discussion: 822 Abbreviations: ADME, absorption, distribution, metabolism and excretion; afe, average fold error; CLr, renal clearance; CLp, plasmatic clearance; fu, unbound plasma fraction; GFR, glomerular filtration rate; KBF, kidney blood flow; NSAID, non-steroidal anti-inflammatory drug; OAT, organic anion transporter; OATP, organic anion transport protein; PPB, plasma protein binding; rmse, root mean square error. DMD # 37267 Abstract Identifying any extra-hepatic excretion phenomenon in preclinical species is crucial for an accurate prediction of the pharmacokinetics in man. This is particularly the case for drugs with a small volume of distribution, as they require an especially low total clearance in order to be suitable for a once-a-day dosing regimen in man. In this study, three animal scaling techniques were applied for the prediction of the human renal clearance of 36 diverse drugs that show active secretion or net re-absorption