Relatively New Thoughts on the Oldest Clinical Pharmacology Parameter: Half-Life
Presented by: Leslie Benet, Ph.D., UCSF
Thursday, February 20, 2020
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Half-life (t½) is the oldest but least wphell understood pharmacokinetic parameter, because most definitions are related to a hypothetical 1-compartment body model that will not describe most drugs in humans. Alternatively, terminal half-life (t½,z) is utilized as the single defining t½ for most drugs. However, accumulation at steady-state may be markedly over-predicted utilizing t½,z. We defined a new parameter, the “operational multiple dosing half-life” (t½,op), as equal to the dosing interval where at steady-state the maximum concentration will be twice the maximum concentration for the first dose, independent of the route of administration, for drugs following linear kinetics. A simple methodology will be presented to predict the steady-state systemic concentrations for any dosing interval knowing the pharmacokinetics of a single dose and to select the appropriate dosing interval, eliminating the need for the multiple clinical studies frequently undertaken to select the dosing interval for a new molecular entity. The t½,op is compared with previously proposed methodologies for predicting accumulation.
About the Speaker:
||Dr. Leslie Benet, Professor and former Chairman (1978-1998) of Bioengineering and Therapeutic Sciences, University of California San Francisco (UCSF), received his AB, BS and MS from the University of Michigan, and PhD from UCSF. He has received nine honorary doctorates, five from Europe and four from the US, most recently the University of Lisbon in 2016. Dr. Benet served as President of the Academy of Pharmaceutical Sciences (1985) and as first President of the American Association of Pharmaceutical Scientists (1986). In 1987 he was elected to membership in the National Academy of Medicine of the US National Academy of Sciences. He previously served as the Treasurer of ISSX, Chair of the Drug Metabolism Gordon Conference, and in 2015 received the ISSX North American Achievement Award. Dr. Benet has published over 590 scientific articles and book chapters, holds 12 patents and served as editor of 7 books. He is one of the most highly cited drug metabolism scientists world-wide with an H factor of 82 on Clarivate Analytics with >28,000 citations, while on Google Scholar, H=98 and >61,000 citations. Jashvant (Jash) Unadkat, Ph.D. is the Milo Gibaldi Endowed Professor at the School of Pharmacy, University of Washington, Seattle. He received his Bachelor degree in Pharmacy (B.Pharm.) from the University of London (1977), his Ph.D. from the University of Manchester (1982; advisor Prof. Malcolm Rowland) and his postdoctoral training at the University of California at San Francisco (1982-85; advisor the late Dr. Lewis B. Sheiner). |