Table 5

Pharmacokinetic parameters of depsipeptide (FR901228) of two-compartment open model (A) and noncompartmental analysis (B)

A. Dosea (mg/m2)CLb (liters/h/m2)T1/2α (h)T1/2β (h)Vc (liters/m2)Cmax (ng/ml)
1.0 (n = 3, c = 5)8.8 ± 4.50.24 ± 0.148.3 ± 13.43.7 ± 2.635.6 ± 22.2
1.7 (n = 3, c = 5)12.0 ± 7.50.61 ± 0.3849.5 ± 58.69.2 ± 3.440.8 ± 20.9
2.5 (n = 3, c = 6)21.6 ± 17.60.48 ± 0.6816.1 ± 31.29.3 ± 10.149.5 ± 31.7
3.5 (n = 1, c = 2)10.6 ± NA0.63 ± NA9.5 ± NA10.5 ± NA129.9 ± NA
6.5 (n = 3, c = 5)10.5 ± 2.20.30 ± 0.116.6 ± 2.25.0 ± 1.6211.8 ± 77.1
9.1 (n = 4, c = 7)c21.7 ± 11.41.20 ± 2.319.0 ± 24.510.5 ± 13.5162.6 ± 53.8
12.7 (n = 3, c = 5)38.2 ± 26.40.26 ± 0.2012.7 ± 9.120.7 ± 20.2224.7 ± 241.0
17.8 (n = 11, c = 19)11.6 ± 5.80.42 ± 0.258.1 ± 6.08.6 ± 6.3553.8 ± 299.5
24.9 (n = 8, c = 12)19.2 ± 10.60.34 ± 0.184.3 ± 2.38.6 ± 3.3478.2 ± 316.6
B. Dosec (mg/m2)nAUC0-t (μg/ml/h)AUC0-inf (μg/ml/h)T1/2 (h)Vdss (liters/m2)CLtot (liters/h/m2)
1.030.13 ± 0.090.14 ± 0.1011.2 ± 14.948.8 ± 65.510.2 ± 6.9
1.730.15 ± 0.070.16 ± 0.0714.4 ± 9.838.5 ± 27.021.5 ± 9.7
2.530.12 ± 0.110.12 ± 0.112.3 ± 2.938.5 ± 27.035.4 ± 26.5
3.510.23 ± NA0.24 ± NA11.8 ± NA37.9 ± NA14.7 ± NA
6.530.52 ± 0.060.53 ± 0.068.1 ± 3.718.8 ± 3.712.5 ± 1.4
9.140.75 ± 0.500.79 ± 0.4920.6 ± 16.3126.8 ± 155.014.5 ± 7.4
12.7d10.35 ± NA0.35 ± NA8.5 ± NA55.3 ± NA34.1 ± NA
17.892.21 ± 1.352.27 ± 1.3411.7 ± 8.737.1 ± 43.810.5 ± 6.4
24.981.94 ± 1.501.95 ± 1.527.5 ± 5.520.4 ± 8.318.5 ± 10.1
  • a Values, mean ± SD from cycles 1 and 2.

  • b CL, systemic clearance; T1/2α, distribution half-life; T1/2β, elimination half-life; Vc, volume of distribution of central compartment; Cmax, observed maximum concentration; n, number of patients per dose group (patients who had a dose reduction with the second cycle; the data is reflected for both cycles); c, number of pharmacokinetic profiles per dose group; Vss, volume of distribution at steady state; AUC0-t, AUC time curve (0 to the last measurable concentration time point); AUC0-inf, AUC time curve (0 to infinity).

  • c One patient from the dose group was excluded from the toxicity evaluation; Values, mean ± SD from cycle 1.

  • d Pharmacokinetic profile was not available from 2 patients in the dose group.