An Open-Label, Non-Randomized, Single-Center Study to Determine the Metabolism and Elimination of 14C-E7080 in Patients With Advanced Solid Tumors or Lymphomas, Who Are Unsuitable For, or Have Failed, Existing Therapies.

Maximum Plasma Concentration (Cmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Individual blood/plasma concentration-time data were analyzed using 'non-compartmental' analysis. Cmax was determined from visual inspection of the individual blood/plasma concentration-time profile and was summarized as the Geometric Mean and percent coefficient of variation for the Geometric Mean (CV%) for all participants and expressed as nanograms/milliliter (ng/mL).

Area Under the Plasma Concentration-Time Curve From Time Zero to Time t (AUC(0-t))

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The AUC(0-t) was calculated by the combination of linear/log (from Tmax) trapezoidal rule where 't' is the time of last quantifiable plasma concentration following dosing. AUC(0-t) was summarized as the Geometric Mean (CV%) for all participants and expressed in nanograms·hour/milliliter (ng·hr/mL).

Terminal Phase Rate Constant (λz) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The terminal phase rate constant represents the rate at which study drug was eliminated from the body and was determined by log-linear regression of the plasma concentrations against time in the terminal phase and was summarized as the Geometric Mean (CV%) for all participants and expressed as 1/hours.

Terminal Exponential Half-life (t1/2) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib in Plasma

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The terminal phase t1/2 is the time required to divide the plasma concentration of study drug by two after reaching pseudo-equilibrium, and not the time required to eliminate half of the administered dose of study drug. The t1/2 during the apparent terminal disposition phase was calculated at 0.693/λz and was summarized as the Geometric Mean (CV%) for all participants and expressed as hours.

Time of Maximum Plasma Concentration (Tmax) of Radiolabeled 14^C-Lenvatinib and Non-Radiolabeled Lenvatinib

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Individual blood/plasma concentration-time data were analyzed using 'non-compartmental' analysis. Tmax was determined from visual inspection of the individual blood/plasma concentration-time profile and was summarized as the Geometric Mean (CV%) for all participants and expressed as hours.

Renal Clearance of Lenvatinib (CLr)

时间窗: Pre-dose, post-dose at 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours

CLr was determined based on the interval amount and cumulative amount of the analyte excreted in the urine divided by its corresponding AUC over the same collection interval. Aeurine(0-t)/AUC(0-t), where t is the last measurable concentration, was calculated for lenvatinib only and was summarized as the Geometric Mean (CV%) for all participants and expressed in L/hr.

Percentage Recovery of 14^C- Lenvatinib Related Material in the Urine

时间窗: Pre-dose, post-dose at 0-6, 6-12, 12-18, 18-24, 24-30, 30-36, 36-42, 42-48, 48-72, 72-96, 96-120, 120-144, and 144-168 hours

Urine samples were collected at specific time points, then analyzed for the amount of 14\^C- lenvatinib related material. The total radioactive dose of 14\^C-lenvatinib excreted in urine (Aeurine%) was calculated from the time of dosing to the last quantifiable measurement. If radioactivity levels were still present at the end of the Study Phase, sampling continued until each sample contained less than 1% of the total radioactive dose. Percentage recovery of 14\^C- lenvatinib related material in the urine was summarized as the Geometric Mean (CV%) percent cumulative for all participants and expressed as percent of 14\^C- lenvatinib.

Percentage Recovery of 14^C- Lenvatinib Related Material in the Feces

时间窗: Day 1 to Day 8

Fecal samples were collected at specific time points, then analyzed for the amount of 14\^C- lenvatinib related material. The percentage of the 14\^C- lenvatinib dose excreted in feces (Aefeces%) was calculated from time of dosing to the last quantifiable measurement. If radioactivity levels were still present at the end of the Study Phase, sampling continued until each sample contained less than 1% of the total radioactive dose. Percentage recovery of 14\^C- lenvatinib related material in the feces was summarized as the Geometric Mean (CV%) percent cumulative for all participants and expressed as percent of 14\^C- lenvatinib.

Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC(0-inf))

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The AUC(0-inf) was calculated as AUC(0-t) + Ct/λz where Ct is the last measurable concentration and was summarized as the Geometric Mean (CV%) for all participants and expressed in ng·hr/mL.

Percentage of Area Under the Plasma Concentration Curve Extrapolated to Infinity (%AUC(Extra))

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. %AUC(extra) was calculated as \[(AUC(0-inf) - AUC(0-t)/AUC(0-inf) \]\*100 and was summarized as the Geometric Mean (CV%) for all participants and expressed in (ng·hr/mL).

Apparent Clearance (CL/F) of Lenvatinib From Plasma

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. The CL/F for parent lenvatinib only was calculated as Dose/\[AUC(0-inf)\] and was summarized as the Geometric Mean (CV%) for all participants and expressed in L/hr.

Apparent Terminal Volume of Distribution in the Terminal Phase of Lenvatinib (Vz/F)

时间窗: Day 1 (pre-dose, post-dose at 15 and 30 minutes, 1, 2, 4, 6, 8 and 12 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours), Day 5 (96 hours), Day 6 (120 hours), Day 7 (144 hours) and Day 8 (168 hours)

Blood samples were drawn at specific time points then analyzed for the amount of 14\^C-lenvatinib and non-radiolabeled lenvatinib in the plasma. Vz/F for lenvatinib only was calculated as Dose/\[(λz)·(AUC(0-inf))\] and was summarized as the Geometric Mean (CV%) for all participants and expressed in liters (L).