Pharmacokinetic Characterization
Following oral administration of a single dose under fasted conditions, giredestrant was rapidly absorbed with a median time to maximum concentration (tGiredestrant single-dose pharmacokinetic parameters (escalation cohorts)NOTE: Data reported as geometric mean (% CV), except TAbbreviations: AUCGiredestrant mean (±SD) plasma concentration–time profiles after a single dose.Dose proportionality of giredestrant dose-normalized exposure. Abbreviations: AUCGiredestrant steady-state pharmacokinetic parameters (escalation cohorts)NOTE: Data reported as geometric mean (% CV), except TAbbreviations: AR, accumulation ratio; C


At the clinical dose of 30 mg, the geometric mean [geometric % coefficient of variation (%CV)] of maximum steady-state concentration (CMetabolite identification from plasma samples suggested that glucuronidation and oxidation are potentially the metabolism pathways for giredestrant (Genentech data on file). No abundant metabolites or long-lived circulating metabolites were identified; specifically, no major oxidation metabolites were seen.Exploratory assessments of giredestrant concentrations in urine samples over an 8-hour collection period postdose at steady state (cycle 2 day 1) indicated that 0.246% of drug was excreted in urine. Therefore, renal excretion is unlikely to be the major elimination route for giredestrant.