Article Figures & Data
Figures
- Fig. 1.
Chemical structure of [14C]verinurad.
- Fig. 2.
Cumulative percent of radioactive dose recovered in urine and feces at specified intervals after administration of a single 10-mg (500 μCi) oral dose of [14C]verinurad.
- Fig. 3.
Mean (S.E.) concentration-time profiles of verinurad in plasma and total radioactivity in blood and plasma following a single oral dose of 10 mg oral solution with 500 μCi of [14C]verinurad (0–144 hours postdose). Only n = 2 and n = 1 samples were available, respectively, at 96 and 144 hours for total radioactivity in the plasma and blood.
- Fig. 4.
Verinurad and metabolites in pooled plasma, pooled urine, and pooled feces.
- Fig. 5.
The proposed metabolic pathway of verinurad in humans.
- Fig. 6.
Formation of M4 (A) and M8 (B) by recombinant P450s, FMO, and HLM.
- Fig. 7.
Inhibition of M4 formation in HLM by specific chemical inhibitors of CYP3A4 (ketoconazole) and CYP2C9 (sulfaphenazole).
- Fig. 8.
Formation of M1 (A) and M8 (B) metabolites by recombinant glucuronyl transferases. Data are mean (±S.D.) of triplicate samples.
Tables
Analytes MS/MS Transition (m/z, amu) Verinurad 349 → 263 [D6]Verinurad 355 → 263 M4 365 → 279 [D6]Verinurad M4 371 → 279 M1 525 → 263 [D6]Verinurad glucuronide M1 531 → 263 M8 541 → 279 [D6]Verinurad glucuronide M8 547 → 279 amu, Atomic mass unit.
- TABLE 2
Summary of pharmacokinetic parameters (geometric mean, confidence interval 95%) of verinurad in blood and plasma following a single oral dose of [14C]verinurad (10 mg, 500 μCi) given to healthy male subjects
Analyte Matrix Tmaxa Cmax AUC∞ CL/F Vss/F t1/2 CLr0–96 h h ng/ml ng·h/ml l/h l h ml/min Verinurad (N = 8) Plasma 0.50 (0.50–0.75) 160 (117–219) 193 (152–246) 51.8 (40.7–65.9) 504 (368–690) 14.8 (11.9–18.4) — Urine — — — — — — 11.5 (7.64–17.3) Total radioactivityb (N = 8) Plasma 0.50 (0.50–0.75) 344 (255–465) 906 (742–1110) — — 34.7 (26.9–44.7) — Blood 0.50 (0.25–0.75) 190 (144–250) 556 (428–723) — — 37.5 (19.9–70.6) — Blood-to-plasma ratio — 0.551 (0.527–0.576) 0.614 (0.535–0.703) — — — — Plasma verinurad-to-total radioactivity — 0.464 (0.433–0.496) 0.213 (0.194–0.234) — — — — - TABLE 4
Summary of pharmacokinetic parameters (geometric mean, confidence interval 95%) for M1 and M8
Analyte Tmaxa Cmax AUClast AUC∞ t1/2 CLr0–96 h h ng/ml ng·h/ml ng·h/ml h ml/min M1 (N = 8) 0.5 (0.50–0.75) 189 (112–320) 287 (182–452) 290 (185–455) 12.9 (10.2–16.4) 224 (182–276) M1-to-verinurad ratio — 0.786 (0.606–1.02) 1.01 (0.769–1.34) 0.997 (0.761–1.31) — — M1-to-total radioactivity ratio — 0.550 (0.428–0.705) 0.340 (0.252–0.459) 0.321 (0.238–0.432) — — M8 (N = 8) 0.75 (0.50–0.75) 120 (102–142) 273 (227–329) 283 (235–342) 18.1 (12.4–26.5) 338 (286–399) M8-to-verinurad ratio — 0.485 (0.381–0.617) 0.936 (0.769–1.14) 0.943 (0.777–1.14) — — M8-to-total radioactivity ratio — 0.350 (0.282–0.433) 0.324 (0.290–0.361) 0.313 (0.279–0.351) — — AUC∞, area under the plasma concentration-time curve from zero to infinity; (t1/2, half-life;
↵a Tmax is expressed as median (range).
Data Supplement
- Supplemental Data -
Supplemental Material
Supplemental Table 1 - Chemical Names and Structures of Verinurad and its Metabolites Observed in Healthy Adult Male Subjects
- Supplemental Data -
