Table 3.

Summary of ES-285 pharmacokinetics (first course)

Dose (mg/m2)Cmax (ng/mL)AUC (ng h/mL)t1/2 (h)Cl (L/h)Cl (L/h/m2)Vss (L/m2)
4 (n = 0)*
8 (n = 1)*38417163962,010
16 (n = 1)*4995274161472
32 (n = 4)11 (7–18)199 (134–224)5 (2–7)335 (286–455)169 (143–239)837 (234–2,009)
64 (n = 3)27 (17–39)459 (387–525)17 (14–20)289 (256–342)143 (122–171)1,270 (1,013–1,428)
128 (n = 3)69 (49–100)1,244 (1,056–1,438)34 (29–37)187 (160–206)104 (89–121)1,908 (1,292–2,433)
200 (n = 3)91 (86–100)2,238 (1,963–2,457)37 (30–48)198 (158–245)91 (83–102)2,753 (2,139–3,527)
256 (n = 4)106 (91–124)2,486 (1,189–3,510)28 (21–32)257 (109–456)123 (73–217)2,611 (1,615–4,051)
Mean (n = 19)N/AN/A222541281,793

NOTE: Values are expressed as median (range).

Abbreviations: AUC, area under the plasma drug concentration_time curve; Cl, clearance; Cmax, maximum plasma drug concentration following single infusion; N/A, not applicable; t1/2, terminal phase half_life; Vss, volume of distribution at steady state.

  • *Plasma drug concentrations in 10 patients treated with 4 to 16 mg/m2 ES_285 were low and frequently undetectable, thus precluding any meaningful noncompartmental evaluation.