Bioavailability and pharmacokinetic features of etoposide in childhood acute lymphoblastic leukemia patients

The bioavailability and pharmacokinetic characteristics of etoposide were s tudied in 12 relapsed B-lineage acute lymphoblastic leukemia (ALL) patients after both intravenous (i.v.) infusion and oral administration. Following a 1 hour i.v. infusion of 50 mg/m(2) etoposide, the elimination half-life r anged from 49.8 min to 509.4 min (mean +/- SD = 218.6 h +/- 134.7 min), the NMT ranged from 71.8 to 734.9 rain (mean SD = 315.4 +/- 194.3 min) and the systemic clearance of etoposide ranged from 15.7 to 38.0 ml/min/m(2) (mean SD = 24.1 +/- 7.0 ml/min/m(2)). The AUC ranged from 2234.9 to 5427.0 muM(. )min) (mean SD 3827.8 +/- 1069.5 muM(.)min) and Vc ranged from 2026.9 to 13 505.2 ml/m(2) (mean SD 6825.4 +/- 3278.5 ml/m(2)). The maximum plasma etopo side levels ranged from 6.0 to 28.4 muM (mean +/- SD = 13.6 +/- 6.3 EM). Th e bioavailability of oral etoposide was determined by comparing the AUC fol lowing i.v. infusion to the AUC following oral administration in the same p atient. The overall bioavailability (mean +/- SD) was 60.6 +/- 22.4% (range d from 17.6% to 91.2%). The elimination half-life following oral administra tion (mean +/- SD) was 209.8 +/- 196.3 min (ranged from 51.0 to 794.2 min). The time required to reach the maximum plasma etoposide concentration was 145.4 +/- 118.7 min (ranged from 23.7 to 396.9 min). To our knowledge, this is the first report concerning the bioavailability of etoposide in pediatr ic leukemia patients. All of the other pharmacokinetic properties of etopos ide in pediatric B-lineage ALL leukemia patients reported here were similar to those described previously.