Table 1 Summary of pharmacokinetic parameters of GK-667, ICRF-193 and ICRF-193met in rabbits determined by non-compartmental analysis.

From: Development of water-soluble prodrugs of the bisdioxopiperazine topoisomerase IIβ inhibitor ICRF-193 as potential cardioprotective agents against anthracycline cardiotoxicity

 

Cmax (µM)

Tmax (min)

AUClast (h∙µM)

AUCtot (h∙µM)

AUMClast (h2∙µM)

AUMCtot (h2∙µM)

λz (h−1)

t1/2 (h)

MRT (h)

CL (L h−1 kg−1)

Vz (L kg−1)

Vss (L kg−1)

GK-667

2.7

5

–

–

–

–

–

–

–

–

–

–

(0.61–7.4)

(5–5)

–

–

–

–

–

–

–

–

–

–

ICRF-193

11.0

5

4.4

4.4

2.9

3.0

0.94

0.78

0.69

1.9

2.2

1.3

(9.0–12.5)

(5–5)

(3.5–5.3)

(3.6–5.3)

(1.8–4.0)

(2.1–4.1)

(0.55–1.1)

(0.66–1.3)

(0.59–0.92)

(1.6–2.3)

(1.5–3.4)

(1.0–1.7)

ICRF-193met

0.83

120

2.6

2.7

6.5

7.1

0.52

1.4

2.6

–

–

–

(0.54–1.8)

(20–120)

(1.9–3.6)

(1.9–3.8)

(4.3–11.4)

(4.5–13.5)

(0.36–0.63)

(1.1–1.9)

(1.9–3.6)

–

–

–

  1. Cmax observed maximum plasma concentration, Tmax time to reach maximum plasma concentration, AUClast area under the concentration-time curve from zero up to the last quantifiable concentration, AUCtot area under the concentration-time curve from zero up to ∞ with extrapolation of the terminal phase, AUMClast area under the first moment of the concentration-time curve from zero to the last quantifiable concentration, AUMC area under the first moment of the concentration-time curve from zero up to ∞ with extrapolation of the terminal phase, λz terminal rate constant of elimination, t1/2 terminal half-life, MRT mean residence time, CL total clearance, Vz apparent volume of distribution during terminal phase of elimination, Vss apparent volume of distribution at equilibrium.
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